Received Rescue Medication Research Articles

Dapagliflozin monotherapy in drug‐naïve patients with diabetes: a randomized‐controlled trial of low‐dose range

Many patients with type 2 diabetes are suboptimally managed with currently available therapies. Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, has shown efficacy in reducing diabetic hyperglycaemia. This study assessed efficacy of three lower doses in recently diagnosed patients. This phase 3, randomized, double-blind, placebo-controlled study assigned treatment-naïve patients to placebo or dapagliflozin monotherapy (1, 2.5 or 5 mg) daily for 24 weeks. Patients were antidiabetic drug-naïve with inadequate glycaemic control [haemoglobin A1c (HbA1c) ≥7.0 and ≤10.0%]. The primary efficacy endpoint was change in HbA1c from baseline. Secondary endpoints included changes in body weight and fasting plasma glucose (FPG), and proportions achieving HbA1c <7%. A total of 282 patients with type 2 diabetes were randomly assigned to one of four treatment groups. Baseline characteristics were similar across groups. At week 24, mean HbA1c reduction was significantly greater with dapagliflozin: -0.68% for 1 mg, -0.72% for 2.5 mg, -0.82% for 5 mg, versus 0.02% for placebo (p < 0.0001); compared to mean baseline values of 7.8-8.1%. Mean FPG reduction was significantly greater for all dapagliflozin groups versus placebo (p < 0.02), as was mean weight reduction (p < 0.003). During the treatment period, 19.1% of placebo-treated patients received rescue medication or discontinued because of poor glycaemic control versus 6.9, 4.1 and 5.9% for dapagliflozin 1, 2.5 and 5 mg, respectively. Percentages of patients experiencing ≥1 adverse event were similar across groups. Dapagliflozin at doses of 1, 2.5 and 5 mg/day is effective in reducing glycaemic levels and body weight in treatment-naïve patients with type 2 diabetes. Dapagliflozin was generally well tolerated. This insulin-independent mechanism suggests a new treatment for type 2 diabetes.

An open-label extension study evaluating the safety and efficacy of romiplostim for up to 3.5 years in thrombocytopenic Japanese patients with immune thrombocytopenic purpura (ITP)

Long-term use of the thrombopoietin mimetic romiplostim was examined in Japanese patients with chronic immune thrombocytopenic purpura (ITP) in this open-label extension. The starting dose of romiplostim was the previous trial dose or 3 μg/kg/week, which was titrated up to 10 μg/kg/week to maintain platelet counts between 50 and 200 × 10(9)/L. As of April 2010, 44 patients had enrolled; 71 % women, median age 55.5 years, with five patients discontinuing romiplostim due to patient request (2), administrative decision (2), or not achieving study-defined platelet response (1). Median treatment duration was 100 weeks; median average weekly dose was 3.8 μg/kg. Twenty-eight patients (64 %) self-injected romiplostim. The most frequent adverse events were nasopharyngitis and headache. Nine patients (20 %) had a total of 14 serious adverse events (0.31/100 patient-weeks); of these, only oral hemorrhage was considered treatment related. Fifty hemorrhagic adverse events were reported in 20 patients (46 %) (1.12/100 patient-weeks). Ninety-six percent of patients had a platelet response (doubling of baseline platelet count and platelet count ≥ 50 × 10(9)/L). Of the 25 patients receiving concurrent ITP therapy at baseline, all reduced or discontinued the therapy. Eight patients (18 %) received rescue medications. Administration of up to 3.5 years of romiplostim increased platelet counts and was well tolerated in Japanese patients with chronic ITP.

Stimulant Laxatives for the Treatment of Chronic Constipation: Is it Time to Change the Paradigm?

Stimulant Laxatives for the Treatment of Chronic Constipation: Is it Time to Change the Paradigm?

Platelet Function and Activation in Patients with Immune Thrombocytopenia Treated with Eltrombopag: Comparison with Steroid-Treated and Untreated Patients,

Abstract 3280▪▪This icon denotes a clinically relevant abstract Background:Eltrombopag has recently been approved for treatment in immune thrombocytopenia (ITP). Studies on platelet function in eltrombopag-treated patients in comparison to steroid-treated or untreated ITP patients are not available. Objectives:To assess the function of eltrombopag-induced platelets, we compared platelets from eltrombopag-treated patients to those from ITP patients treated with steroids and a group of patients without treatment in a prospective study (ClinicalTrials.gov number NCT00888901). Patients/Methods:We compared platelet function in patients treated with eltrombopag after treatment-induced platelet rise (group 1) to those under steroid treatment (group 2) and ITP patients without treatment (group 3) in a non-randomized prospective study. Platelet function was assessed by adhesion under high shear conditions (surface coverage, SC), P-selectin expression, and formation of platelet-monocyte aggregates (PMA) after treatment induced platelet rise or, in group 3, in patients with ITP without treatment and platelet count between 50–100×109/L at the time of inclusion. Data are given as median [quartiles]. Correlations of the outcome measures are described by the Spearman correlation coefficient. In case of normally distributed data, analysis of variance (ANOVA) and of covariance (ANCOVA) models and in case of non-normally distributed parameters the nonparametric Kruskal-Wallis test were used to compare the groups Results:Eleven patients (female=9) were included in the treatment group with eltrombopag (group 1), thirteen (female=5) in the steroid treatment (group 2) and 6 patients as untreated controls (group 3). None of these patients developed severe bleeding during the study period, none received rescue medication. Four/30 patients were not included in the final analysis, three because they had no treatment induced platelet rise (1 on eltrombopag and 2 on steroids) and 1 because of aspirin medication. Thus, ten patients on eltrombopag, ten patients on steroid treatment and 6 untreated patients were evaluated in the comparative analyses of platelet function. Platelet counts [x109/L] were 48.25 [45.00–59.00] in group 1 after eltrombopag-induced platelet rise, 82.75 [78.50–112.00] in group 2 and 69.25 [65.00–73.00] in group 3. SC was highest in steroid-treated patients (11.25% [8.10–14.00%]) compared to eltrombopag-treated (5.80% [1.80–9.00%]) and untreated (5.03% [3.80–6.20%]) patients and correlated significantly with the platelet count (r=0.72, p<0.0001). There were no differences in P-selectin expression [GeoMFI] (1.15 [0.47–2.77] in group 1, 0.27 [0.10–0.99] in group 2 and 0.59 [0.47–1.44] in group 3; p=0.34) and PMA levels (6.19% [3.91–21.39%] in group 1, 9.73% [1.88–13.29%] in group 2, and 6.56% [4.82–8.43%] in group 3; p=0.93) between the groups. Two patients developed venous thromboses during eltrombopag treatment. No characteristic alteration of platelet function and activation was identified in those 2 patients when compared to the other eltrombopag-treated patients. Conclusions:We proofed a good functional competence of eltrombopag-induced platelets. No substantial hyper-reactivity of eltrombopag-induced platelets in comparison to those of steroid-treated and untreated patients was determined. Disclosures:Pabinger:GlaxoSmithKline: Research Funding, Speakers Bureau. Panzer:GlaxoSmithKline: Speakers Bureau.

GI Stasis in Critical Care Patients: Rescue with Methylnaltrexone and Influence on Laxation, Enteral Feeding and Residual Gastric Volume

Purpose: Bowel stasis is a common problem in the critical care patient. Restoration of normal GI function is essential for establishing enteral feeding, protects against bacterial translocation leading to sepsis, alleviates GI discomfort due to constipation and shortens ICU residence. The majority of critical care patients are sedated with opioids which contribute to GI stasis. There is a pressing need for a benign therapy that will rapidly rescue these patients without interference with the beneficial actions of these drugs. The present study followed patients over a six week period in our ICU that required rescue medication for GI stasis and compared standard rescue therapy with methylnaltrexone (MNTX), a quaternary ammonium compound that antagonizes peripheral opiate receptors but does not cross the blood-brain barrier. Methods: This was a retrospective chart review of 88 non-surgical critical care patients, 15 of whom met the criteria of failure to open bowels within 72 hours despite standard treatment with senna and sodium docusate. Eight of these patients received rescue medication consisting of ½ sachet picolax plus 2 glycerin suppositories. Seven patients received MNTX (s.c. 0.15mg/kg). All patients continued on the existing senna/docusate. A separate clinician in collaboration with the nursing staff recorded the response to treatment. A responder was defined as laxation within 24 hours. Additional measures included time to opening of bowels following rescue medication, tolerance of nasogastric feed, sedation score and requirements. Results: The two groups were well matched for age, APACHE II score and agitation score. Fentanyl dose was slightly greater in the MNTX group (178.6 ± 85.9 vs 150 ± 75.6 μg/hr, n.s.). The MNTX group was receiving twice the mean dose of norepinephrine (0.24 ± 0.14 vs 0.11 ± 0.08 mg/kg/min, p=0.04). Six of seven (85%) MNTX patients responded with laxation within 24 hours versus 0/8 (0%) for standard therapy (p=0.001). The median time to laxation was 30.7 ± 60.92 vs 96 ± 18.2 hr (p=0.022). All MNTX patients but only 50% of patients on standard therapy went on to enteral feeding. Of these, mean residual gastric volumes were 7.1 ± 18.9 ml vs 216.3 ± 235.7 ml (n.s.) in the MNTX and standard groups, respectively. Mortality was 2/7 for MNTX vs 4/8 for standard therapy. Conclusion: Although this is a small cohort of patients, the differences in outcome were nevertheless statistically significant in favor of MNTX. This study shows that not only does this opioid antagonist rapidly produce laxation in critical care patients, it also shortens the progression time to enteral feeding and reduces residual gastric volumes. Methylnaltrexone appears to relieve stasis in both the upper and lower GI tract of critical care patients.

Local allergic rhinitis: Allergen tolerance and immunologic changes after preseasonal immunotherapy with grass pollen

Local allergic rhinitis: Allergen tolerance and immunologic changes after preseasonal immunotherapy with grass pollen

Ibuprofen provides analgesia equivalent to acetaminophen-codeine in the treatment of acute pain in children with extremity injuries: A randomized clinical trial

Objectives: This study compared the analgesic effectiveness of acetaminophen–codeine with that of ibuprofen for children with acute traumatic extremity pain, with the hypothesis that the two medications would demonstrate equivalent reduction in pain scores in an emergency department (ED) setting. Methods: This was a randomized, double-blinded equivalence trial. Pediatric ED patients 5 to 17 years of age with acute traumatic extremity pain received acetaminophen–codeine (1 mg/kg as codeine, maximum 60 mg) or ibuprofen (10 mg/kg, maximum 400 mg). The patients provided Color Analog Scale (CAS) pain scores at baseline and at 20, 40, and 60 minutes after medication administration. The primary outcome measured was the difference in changes in pain score at 40 minutes, compared to a previously described minimal clinically significant change in pain score of 2 cm. The difference was defined as (change in ibuprofen CAS score from baseline) – (change in acetaminophen–codeine CAS score from baseline); negative values thus favor the ibuprofen group. Additional outcomes included need for rescue medication and adverse effects. Results: The 32 acetaminophen–codeine and the 34 ibuprofen recipients in our convenience sample had indistinguishable pain scores at baseline. The intergroup differences in pain score change at 20 minutes (−0.6, 95% confidence interval [CI] = −1.5 to 0.3), 40 minutes (−0.4, 95% CI = −1.4 to 0.6), and 60 minutes (0.2, 95% CI = −0.8 to 1.2) were all less than 2 cm. Adverse effects were minimal: vomiting (one patient after acetaminophen–codeine), nausea (one patient after ibuprofen), and pruritus (one after acetaminophen–codeine). The three patients in each group who received rescue medications all had radiographically demonstrated fractures or dislocations. Conclusions: This study found similar performance of acetaminophen–codeine and ibuprofen in analgesic effectiveness among ED patients aged 5–17 years with acute traumatic extremity pain. Both drugs provided measurable analgesia. Patients tolerated them well, with few treatment failures and minimal adverse effects.

Safety and Efficacy of Romiplostim in Immune Thrombocytopenia (ITP) in the “real-life” : Result of the French Experience in 72 Adults.

Abstract 3519Poster Board III-456 IntroductionRomiplostim is a thrombopoietic agent that has been unequivocaly demonstrated as highly effective in adult's ITP in prospective studies and has recently been licensed for adults with chronic ITP in USA, Europe, Canada, and Australia. France has been the only country where romiplostim could be given for a compassionate use outside clinical studies from January 2008. The official indication for obtaining romiplostim in this setting was: chronic ITP according to the international criteria and failure or relapse after at least one previous line of therapy regardless the status towards splenectomy. We report here the data on safety and efficacy of the first consecutive 80 ITP patients who have been registered by the French health authorities as receiving the treatment “off-label” and with at least one-year of follow up. Patients and methodsThe data were retrospectively reviewed using a standardized form. The protocol was approved by local ethical committee. Patients who did not fulfil official indication criteria of compassionate use were excluded (i.e. secondary-ITP). Platelet count was monitored at least monthly during the follow-up. Platelet response was defined as platelet count of 50×109/L or more and a doubling of the pre-treatment count in the absence of any rescue medication within the last 8 weeks. One-year sustained response was defined as a platelet response on at least 2 of the last 3 platelet determinations at month-10-11 and 12. Patients who received rescue medication at any time during the study could not be counted as having a one-year sustained response. Report of adverse events was captured using a standardized form. ResultsAmong the 80 patients, 8 were actually excluded from the analysis (6 with secondary ITP and 2 have been misdiagnosed as having ITP). The analysis was then conducted on 72 patients (43 females) with a median age of 60 years (20 to 91). The median duration of ITP prior to romiplostim administration was 8.7 years (0.1 to 49) and the patients had received a median of 5 (2 to 12) treatment-lines before romiplostim including: corticosteroids (100%), rituximab (65/72, 90%) and splenectomy (39/72, 54%). Among the 33 non-splenectomized patients, 13 patients were reluctant to undergo splenectomy whereas splenectomy was considered as contra-indicated in 20 of them. At time of romiplostim first administration, median platelet count was 16×109/L (1 to 60) and 48 patients (66%) were receiving a concurrent treatment for ITP, including mainly steroids (n=29) ± immunosuppressive drugs (n=8).A platelet response was observed at least once in 76% (55/72) of the patients. On average, patients who responded at any point during the study had a platelet response during 64% of the time (range: 37 to 100%). Romiplostim was stopped in 28 % (20/72) of patients for either lack of efficacy (n=16), for intolerance (n=1) or because it was administered only transiently in preparation for surgery (n=3). Two patients had died respectively from a septic shock and from an ITP-related intracranial hemorrhage. At one-year of follow up, 52 patients were still receiving romiplostim at a median dose of 6.5 μg/kg per week. This dose remained relatively stable as after the first 12 weeks of treatment, romiplostim could be pursued at a stable dose ± 2 μg/kg in 82% of the cases. Twenty % (14/72) of patients received a rescue medication during the study and 50% (36/72) of the patients had a one-year sustained response. The percentage of one-year sustained response was similar in splenectomized and non splenectomized groups [respectively 54% (21/39) and 45% (15/33), NS)]. Among the 29 patients who responded to romiplostim and who were receiving a treatment at time of romiplostim initiation, 86 % (25/29) had discontinued this medication and a further 7% (2/29) had reduced the dose by at least 25%.Only one patient stopped romiplostim because of an adverse event (headache). The most frequent otherwise reported adverse events were: arthralgia (26%), fatigue (13%) and nausea (7%). A transient thrombocytosis > 400×109/L and > 1000×109/L has been observed in respectively 19% (14/72) and 4% (3/72) of patients. A transient stroke occurred in 2 elderly patients (age > 70 yrs). No deep vein thrombosis occurred. Myelofibrosis was not observed. ConclusionOur study confirms in “real-life” that romiplostim is definitely an effective and safe treatment for severe chronic ITP in both non-splenectomized and splenectomized adults. Disclosures:Godeau:AMGEN: Consultancy.

Ibuprofen Provides Analgesia Equivalent to Acetaminophen–Codeine in the Treatment of Acute Pain in Children with Extremity Injuries: A Randomized Clinical Trial

This study compared the analgesic effectiveness of acetaminophen-codeine with that of ibuprofen for children with acute traumatic extremity pain, with the hypothesis that the two medications would demonstrate equivalent reduction in pain scores in an emergency department (ED) setting. This was a randomized, double-blinded equivalence trial. Pediatric ED patients 5 to 17 years of age with acute traumatic extremity pain received acetaminophen-codeine (1 mg/kg as codeine, maximum 60 mg) or ibuprofen (10 mg/kg, maximum 400 mg). The patients provided Color Analog Scale (CAS) pain scores at baseline and at 20, 40, and 60 minutes after medication administration. The primary outcome measured was the difference in changes in pain score at 40 minutes, compared to a previously described minimal clinically significant change in pain score of 2 cm. The difference was defined as (change in ibuprofen CAS score from baseline) - (change in acetaminophen-codeine CAS score from baseline); negative values thus favor the ibuprofen group. Additional outcomes included need for rescue medication and adverse effects. The 32 acetaminophen-codeine and the 34 ibuprofen recipients in our convenience sample had indistinguishable pain scores at baseline. The intergroup differences in pain score change at 20 minutes (-0.6, 95% confidence interval [CI] = -1.5 to 0.3), 40 minutes (-0.4, 95% CI = -1.4 to 0.6), and 60 minutes (0.2, 95% CI = -0.8 to 1.2) were all less than 2 cm. Adverse effects were minimal: vomiting (one patient after acetaminophen-codeine), nausea (one patient after ibuprofen), and pruritus (one after acetaminophen-codeine). The three patients in each group who received rescue medications all had radiographically demonstrated fractures or dislocations. This study found similar performance of acetaminophen-codeine and ibuprofen in analgesic effectiveness among ED patients aged 5-17 years with acute traumatic extremity pain. Both drugs provided measurable analgesia. Patients tolerated them well, with few treatment failures and minimal adverse effects.

Long-term comparison of sublingual immunotherapy vs inhaled budesonide in patients with mild persistent asthma due tograss pollen

Few studies have compared the effects of immunotherapy and inhaled steroids. The main limitation of such studies is the long duration required to fully appreciate the effects of immunotherapy. To compare the effects of inhaled budesonide and sublingual immunotherapy (SLIT) in mild persistent asthma for up to 5 years. Patients with mild persistent asthma and rhinitis due to grass pollen were enrolled in an open randomized controlled trial. After a run-in season, they were randomized to either budesonide, 800 microg/d, in the pollen season or continuous grass SLIT for 5 years. All patients received rescue medications. Symptoms were evaluated by diary cards filled out from May to July at baseline and after 3 and 5 years. In-season nasal eosinophils and bronchial hyperresponsiveness were also assessed. Fifty-one patients were enrolled and 46 completed the study. The bronchial symptom scores and the use of bronchodilators decreased significantly in both groups, but the improvement was greater in the SLIT patients at 3 and 5 years. The nasal symptom score and the intake of nasal steroids decreased only in the SLIT group, and the difference vs the budesonide group was always significant. In the SLIT group vs the budesonide group, a statistically significant decrease of nasal eosinophils was found at 3 and 5 years (P < .01). The bronchial hyperresponsiveness improved significantly only in the SLIT group. In patients with grass pollen-induced asthma, in the long term SLIT was equally effective as inhaled budesonide in treating bronchial symptoms and provided an additional benefit in treating rhinitis symptoms and bronchial hyperresponsiveness.

Ramosetron for the Prevention of Nausea and Vomiting During 5-Fluorouracil-Based Chemoradiotherapy for Pancreatico-biliary Cancer

The aim of the study was to evaluate the role of ramosetron for the prevention of chemoradiotherapy-induced nausea and vomiting (CRINV) in patients receiving upper abdominal irradiation with concurrent 5-fluorouracil chemotherapy. Between November 2006 and April 2007, 25 patients with pancreatico-biliary cancer underwent adjuvant chemoradiotherapy. A total dose of 40 Gy was delivered using 2 Gy/fraction, 5 days a week, with 2 weeks of planned rest after 20 Gy. Concomitant 5-fluorouracil (500 mg/m(2)/day i.v. bolus) was administered for the first 3 days of each split course. During the first course of chemoradiotherapy, all patients had prophylactic metoclopramide before treatment and those refractory to metoclopramide received rescue medication with ondansetron. During the second course of chemoradiotherapy, prophylactic ramosetron was given to patients who were refractory to ondansetron. Response to antiemetics was scored in four tiers: none, no CRINV; mild, did not interfere with normal daily life; moderate, interfered with normal daily life and severe, patient bedridden because of CRINV. Fifty-six percent of the patients (14 of 25) had moderate CRINV despite metoclopramide, and received ondansetron. Ten patients who experienced moderate CRINV despite the ondansetron had prophylactic ramosetron, and 60% of the patients (6 of 10) had the symptom improved. Ramosetron proved to be an effective alternative for the control of CRINV during upper abdominal irradiation with concurrent 5-fluorouracil chemotherapy.

Efficacy and Safety of Vildagliptin Monotherapy during 2-Year Treatment of Drug-naïve Patients with Type 2 Diabetes: Comparison with Metformin

The present study was a 52-week extension of a previously published, multi-center, randomized, parallel-group study. The aim of this extension study was to compare the efficacy and tolerability of vildagliptin and metformin in drug-naïve patients with type 2 diabetes over 104 weeks. The extension population comprised 305 patients randomized to vildagliptin (100 mg daily) and 158 patients randomized to metformin (2 000 mg daily). Pioglitazone was added as rescue medication if fasting glucose was >10 mmol/l; data from patients receiving rescue medication were excluded from the primary analysis. Baseline HbA (1c) averaged 8.4+/-0.1% in patients randomized to vildagliptin and 8.8+/-0.1% in those randomized to metformin. The adjusted mean change from baseline to study endpoint was -1.0+/-0.1% in vildagliptin-treated patients and -1.5+/-0.1% in those receiving metformin (p<0.001 vs. vildagliptin). These results were similar to those reported after the 1-year core phase of the study. The adjusted mean changes in body weight from baseline to endpoint were 0.5+/-0.4 kg and -2.5+/-0.5 kg in the vildagliptin and metformin groups, respectively. One or more adverse event (AE) was reported by 82.2% of patients receiving vildagliptin and by 87.3% of those receiving metformin (p<0.001). Gastrointestinal AEs were more common in patients receiving metformin (45.6%) than in those receiving vildagliptin (25.0%, p<0.001 vs. metformin). One hypoglycemic event occurred after strenuous exercise in a single patient receiving vildagliptin (0.3%). In conclusion, both vildagliptin and metformin monotherapy provided clinically meaningful decreases in HbA (1c) over 2 years in drug-naïve patients with type 2 diabetes. Vildagliptin was weight neutral, while weight loss was observed with metformin; however, metformin was associated with significantly worse gastrointestinal tolerability.

A Phase 2 Open-Label, Sequential-Cohort, Dose-Escalation Study of AMG 531 in Japanese Patients with Chronic Immune Thrombocytopenic Purpura (ITP).

AMG 531 is a novel thrombopoiesis-stimulating peptibody that is being studied for its ability to increase platelet production by stimulating the thrombopoietin (TPO) receptor. This phase 2 study was conducted to identify the appropriate starting dose of AMG 531 for treatment of chronic ITP in adult Japanese patients. The study consisted of 2 phases: a 2-week cohort dose-escalation phase to determine the starting dose for subsequent phase 3 evaluation, and a treatment continuation phase (that lasted until completion of the dose-escalation phase) which provided continuation of treatment for those with a platelet response. Patients in the continuation phase received the dose of AMG 531 they had received in the dose-escalation phase with the option for subsequent dose adjustments. Twelve patients were enrolled with a mean platelet count of 11.8x109/L and a median age of 60.5 years (range 32 to 63); 8 were female. Four patients enrolled into each of 1μg/kg, 3μg/kg, or 6μg/kg dose cohorts and received AMG 531 by subcutaneous injection on days 1 and 8 with no dose adjustments. Cohort dose escalation was to be stopped in the event of an observed platelet count >1000x109/L. Comparison of dose cohorts showed that the proportion of patients achieving a platelet response (doubling of baseline counts and ≥50x109/L) was greater in cohorts receiving higher doses of AMG 531 (see Table). A dose response was also observed in the mean peak platelet counts, the mean fold changes from baseline in peak platelet counts, and the maximum platelet count. Because one patient in the 6μg/kg cohort had an excessively high platelet count (980x109/L), this dose was eliminated from consideration as the starting dose in phase 3 and further dose escalation to 10μg/kg dose cohort was stopped. Five of 7 eligible patients (3μg/kg, 1/4; 6μg/kg, 4/4) elected to enter the treatment continuation phase. There were no study withdrawals, and no serious adverse events (AEs) were reported during the study in either phase. The most common treatment-related AE in the cohort phase was headache (25%), and in the treatment continuation phase were arthralgia, contact dermatitis, and malaise (each 20%). No patients received rescue medications during the entire treatment period. No antibodies against either AMG 531 or endogenous TPO were detected. AMG 531 was well-tolerated and produced a dose-responsive increase in platelet counts. The phase 3 study in Japanese patients with ITP will be initiated with a starting dose of 3μg/kg based on the outcome of this study. [Display omitted]

Evaluation of AMG 531 Efficacy in Splenectomized Patients with Chronic Immune Thrombocytopenic Purpura (ITP) in a Randomized Placebo-Controlled Phase 3 Study.

AMG 531 is a novel thrombopoiesis-stimulating peptibody that acts by stimulating the thrombopoietin (TPO) receptor. We report efficacy data in splenectomized patients from a randomized, double blind, placebo-controlled Phase 3 study designed to evaluate the efficacy and safety of AMG 531 in patients with chronic ITP. Sixty-three splenectomized patients were enrolled (placebo, 21; AMG 531, 42), with a median age of 52 years (range 26 to 88) and a mean baseline platelet count 14.7x109/L. Subcutaneous AMG 531 or placebo was administered weekly for 24 weeks at a starting dose of 1μg/kg, and adjusted to maintain a target platelet count of 50–200x109/L. The primary study endpoint was the incidence of a durable platelet response, defined as a platelet count ≥50x109/L for ≥6 weeks during the last 8 weeks of the 24 week treatment period in the absence of rescue medications. Sixteen of the 42 splenectomized patients (38.1%) receiving AMG 531 achieved a durable platelet response compared to 0/21 (0.0%) receiving placebo (p=0.0013). Overall response, defined as either durable or transient platelet response (≥4 weekly platelet responses), was observed in 33/42 (78.6%) patients receiving AMG 531, compared to 0/21 (0%) placebo patients. The mean number of weekly platelet responses (platelet count ≥50x109/L) was significantly greater in patients receiving AMG 531 (12.3/24 weeks, 51%) compared to placebo (0.2/24 weeks, 1%) (p<0.0001). AMG 531 reduced the proportion of patients requiring ITP rescue medications, defined as either increase from baseline in dose of concurrent medication or use of new medication to increase platelet counts. Twelve of 21 (57.1%) placebo-treated patients received rescue medications compared to just 11/42 (26.2%) AMG 531-treated patients (p=0.0175). In addition, 12/12 (100.0%) AMG 531-treated patients compared to 1/6 (16.7%) placebo-treated patients either discontinued or reduced by >25% their concurrent ITP medications. AMG 531 was well-tolerated. There were 2 treatment-related serious adverse events; 1 patient with elevated bone marrow reticulin that returned to baseline 3 months after withdrawal of AMG 531, and 1 patient experienced thrombosis that was successfully treated allowing study continuation. No patient developed neutralizing antibodies against either AMG 531 or endogenous TPO. In summary, AMG 531 was well-tolerated, and effectively increased and sustained platelet counts in splenectomized patients with ITP. AMG 531-treated patients required less frequent rescue medications in comparison to those receiving placebo, and were able to reduce their use of concurrent therapies.

Evaluation of AMG 531 Efficacy in Nonsplenectomized Patients with Chronic Immune Thrombocytopenic Purpura (ITP) in a Randomized Placebo-Controlled Phase 3 Study.

AMG 531 is a novel platelet-stimulating peptibody that stimulates the thrombopoietin (TPO) receptor, and is being studied for its ability to increase production of platelets. Here we report efficacy data in nonsplenectomized patients from a randomized, double blind, placebo-controlled Phase 3 study designed to evaluate the efficacy and safety of AMG 531 in patients with chronic ITP. Sixty-two nonsplenectomized patients were enrolled (placebo, 21; AMG 531, 41) with a median age of 52 years (range 21 to 88) and a mean baseline platelet count of 18.3x109/L. Subcutaneous AMG 531 or placebo was administered weekly for 24 weeks at a starting dose of 1μg/kg, and adjusted to maintain a target platelet count of 50-200x109/L. One patient randomized to placebo received 3 doses of AMG 531 in error and was included in the efficacy analysis as a placebo. The primary study endpoint was the incidence of a durable platelet response, defined as a platelet count ≥50x109/L for ≥6 weeks during the last 8 weeks of the 24-week treatment period in the absence of rescue medications. Starting at a low dose of AMG 531 and gradually increasing it, as well as reducing the dose of steroids in certain patients, contributed to lower platelet counts early in the study. Twenty-five of the 41 patients (61.0%) receiving AMG 531 achieved a durable platelet response compared to 1/21 (4.8%) receiving placebo (p<0.0001). Overall response, defined as either durable or transient platelet response (≥4 weekly platelet responses), was observed in 36/41 (87.8%) patients receiving AMG 531, but was observed in only 3/21 (14.3%) placebo patients. The mean number of weekly platelet responses (platelet count ≥50x109/L) was significantly greater in patients receiving AMG 531 (15.2/24 weeks, 63%) compared to placebo (1.3/24 weeks, 5%) (p<0.0001). AMG 531 reduced the proportion of patients requiring ITP rescue medications, defined as either increase from baseline in dose of concurrent ITP medication or use of new medication to increase platelet counts. Thirteen of 21 (61.9%) placebo-treated patients received rescue medications compared to just 7/41 (17.1%) AMG 531-treated patients (p=0.0004). There were no treatment-related serious adverse events and no patients tested positive for neutralizing antibodies against either AMG 531 or endogenous TPO. In summary, as in previous studies, AMG 531 was well-tolerated while effectively increasing and sustaining platelet counts in nonsplenectomized patients with ITP. When compared to placebo, AMG 531 administration resulted in a higher mean platelet count, and was associated with less frequent use of rescue medications.

Sumatriptan for the treatment of undifferentiated primary headaches in the ED

Objective In this study, we determine the effectiveness and adverse effects of sumatriptan when used in the emergency department (ED) as a first-line treatment for benign undifferentiated headaches, and determine if the International Headache Society (IHS) classification of migraine, probable migraine, or tension-type headache has any effect on the effectiveness of the treatment. We hypothesize that there is no difference in the effectiveness of pain relief or frequency and severity of adverse effects between patients with migraine, probable migraine, or tension-type headaches when treated with sumatriptan. Methods This was a prospective observational study of adult ED patients undergoing treatment for primary headaches (ie, patients in whom head trauma, vascular disorders, infection, or disorders of facial or cranial structures have been clinically excluded). Other exclusions were renal impairment, hepatic impairment, and risk factors for coronary artery disease. Consenting patients then were asked to complete a 100-mm visual analog scale (VAS) representing their perceived pain, after which they were interviewed by a research assistant who completed a headache diagnosis worksheet, which differentiates the headache by IHS criteria. The patient repeated the VAS score at 30 and 60 minutes. Data were analyzed using descriptive statistics and χ 2 tests. Results One hundred forty-seven patients were enrolled: 84 (57.1%) patients with migraine headache, 45 (30.7%) with a probable migraine headache, and 18 (12.2%) with a tension headache. A 50% reduction in VAS scores 60 minutes postdose was seen in 87 (59%) of 147 patients; 50 (60%) of 84 of migraine patients, 25 (56%) of 45 of probable migraine patients, and 12 (67%) of 18 tension patients ( P = .72). There were no serious adverse events reported. Forty-seven patients (32%) received rescue medications after the 60-minute VAS score: 29 (34.5%) patients in the migraine group, 15 (33.3%) patients in the probable migraine group, and 3 (15.8%) patients in the tension-type headache group ( P = .26). Conclusions Most of the patients presenting with primary headaches had migraine or probable migraine headaches. There was no difference in sumatriptan's effectiveness based on the classification of the headache using IHS criteria.

P.3.017 A double-blind, randomized, placebo-controlled trial of quetiapine augmentation in patients with obsessive-compulsive disorder resistant to serotonin reuptake inhibitors

An increasing number of prescribers are using antipsychotics for treatment of anxiety disorders, despite lack of FDA-approved indications and mixed efficacy results from clinical trials. The objective of this study was to examine the prevalence of antipsychotics prescription in psychiatric inpatients and outpatients with anxiety disorders.This is a retrospective study of de-identified data from patients with a DSMIV-TR anxiety disorder diagnosis in an academic psychiatric setting in 2013. The final cohort of patients, after exclusion of bipolar/psychotic comorbidity, includes 1699 patients. Logistic regression models were used to explore associations between antipsychotic prescription and patient characteristics.Among non-psychotic/non-bipolar patients with anxiety disorder, 53.6% of inpatients and 16.6% of outpatients received antipsychotic medication. Rates varied with the disorder. Outpatients with post-traumatic stress disorder (OR: 2.24, 95% CI: 1.66–3.01) and obsessive compulsive disorder (OR: 2.80, 95% CI: 1.86–4.19) received antipsychotic prescriptions more often than those without these diagnoses. Comorbidity with depression was common while comorbidity with borderline personality disorder was rare; both increased odds of receiving prescription of antipsychotics (OR: 1.57, 95% CI: 1.16–2.12 for depression; OR: 2.63, 95% CI 1.42–4.88 for borderline personality disorder, respectively). Additionally, age was significantly associated with increased odds of being on an antipsychotic. Quetiapine and aripripazole were the most prescribed antipsychotics and very few patients received rescue medication for extrapyramidal symptoms.Lack of specific indications for the psychotropic prescriptions.A substantial percentage of patients with anxiety disorders are prescribed antipsychotics, especially among inpatients. This practice may reflect the severity of the anxiety disorder or the high prevalence of comorbidity. Based on frequency of rescue medication prescription, treatment seemed well tolerated for extra-pyramidal neurological side-effects.

A Retrospective Review of the Use and Safety of Droperidol in a Large, High‐risk, Inner‐city Emergency Department Patient Population

Droperidol (DROP) is used in the emergency department (ED) for sedation, analgesia, and its antiemetic effect. Its ED safety profile has not yet been reported in patients (pts). Objectives: To document the use of DROP in highrisk pts (those with head injury, alcohol or cocaine intoxication, and/or remote or recent seizures), and to determine the number of serious and minor adverse events (AEs)—seizures, hypotension, extrapyramidal side effects (EPSEs)—after DROP. Methods: The ED database (EmSTAT) was queried to determine who received intramuscular or intravenous DROP in the ED in 1998; further chart review was done if the patient was considered high risk for or had experienced an AE. Multiple regression analysis using a random‐effects model determined the significance of each variable in the occurrence of AEs. Results: 2,468 patients (aged 20 months to 98 years; 112 ≤17 years; 141 ≥66 years) received DROP for agitation (n = 1,357), pain (1,135), anxiety (99), vomiting (173), or other reasons (50). There were 945 pts considered high risk; 933 charts were reviewed (DROP mean dose 4.1 ± 2.0 mg); of these, 50 patient visits did not meet the criteria for high risk. There were 622 pts with head trauma (401 with alcohol use), including 47 with computed tomography (CT) scans positive for brain injury, 64 with cocaine use, and 197 with recent or remote seizures (137 with alcohol use). Minor AEs such as transient hypotension occurred in 96 pts after DROP (73 with alcohol use); 20 received intravenous fluids, while an additional 28 pts (8 with alcohol use) received rescue medications for EPSEs. Six possible serious AEs occurred in pts with serious comorbidities; 2 cases of respiratory depression, 3 post‐DROP seizures, and 1 cardiac arrest (resuscitated) 11 hours after DROP in a cocaine‐intoxicated pt (normal QT interval). There was no significant difference among high‐risk groups in the occurrence of AEs. Conclusions: The vast majority of pts who received DROP in the ED did not experience an AE. A few serious AEs were noted following DROP in patients with serious comorbidities; it is not clear that DROP was causative.

Double-blind comparison of alizapride, droperidol and ondansetron in the treatment of post-operative nausea

To compare the efficacy in the treatment of post-operative nausea and/or vomiting (PONV), 75 patients undergoing gynaecological procedures under general anaesthesia using N2O/enflurane who suffered from PONV in the first hour after surgery were randomly allocated to three groups containing 25 patients each to receive either alizapride 100 mg, droperidol 1 mg or ondansetron 8 mg (i.v.). Patients expressed the severity of their nausea on a Visual Analogue Scale (VAS) ranging from 0 (none) to 10 (as bad as possible). Vomiting was recorded as present or absent, and the number of emetic events was noted. Data were recorded until rescue medication was given or until 4 h after the administration of the study drug. There were no significant differences between the three groups in the average VAS scores and the presence of vomiting at the time of entry into the study. Fifteen and 30 min after the administration of the study drug, VAS decreased notably in all groups. This decrease was similar and statistically significant within each group. However, comparison between the three groups showed no statistically significant differences. There was no statistically significant difference between the three groups in the number of patients receiving rescue medication, the number of emetic events and the time from administration of the study drug until rescue medication was given. It is concluded that alizapride 100 mg, droperidol 1 mg and ondansetron 8 mg intravenously are equally effective in the treatment of PONV after gynaecological procedures and that the newer drugs alizapride and ondansetron offer no advantage over droperidol.

Subcutaneous Sumatriptan in Acute Migraine

To the Editor. — Cady et al 1 presented a large and well-designed study of an exciting new drug, sumatriptan, for the treatment of migraine attacks. While the data concerning early relief were truly impressive, the authors largely neglected the problem of recurrences of migraine, and they reviewed the existing therapies for migraine in such a negative way as to suggest ignorance or bad judgment. In the sumatriptan group, 20% of patients received rescue medication in the clinic after 2 hours, and 61% received it within 24 hours. In the placebo-treated group, the percentages were 59% at 2 hours and 88% at 24 hours. It is therefore clear from the data presented that more than half of the sumatriptan-treated patients did not feel sufficient relief within 24 hours. Since initial relief was good, this later failure was most likely due to the recurrence of migraine . Initially, successful treatment of migraine