Single-dose Arm Research Articles

Evaluation of Single Versus Two-Dose Basiliximab Induction Therapy in Live-Donor Liver Transplant.

Basiliximab is a high-cost induction agent typically given as two doses in liver transplant recipients. This study evaluated renal outcomes in live-donor liver transplant recipients (LDLTRs) with stable renal function at the time of transplant receiving one versus two doses of basiliximab. We retrospectively identified 231 adult LDLTR with a serum creatinine (SCr) <1.5mg/dL on post-transplant Day 5. The primary endpoint was a change in SCr from post-transplant Days 5 to 30 between the groups. Secondary endpoints included incidence of acute kidney injury (AKI), liver rejection, and culture-positive infections within 3 and 6 months of transplant. Basiliximab-related cost savings were also evaluated. Median change in SCr from post-transplant Days 5 to 30 was no different between the single-dose or two-dose groups (0.1 [IQR: -0.1-0.3] vs. 0.2 [IQR: -0.1-0.4], p = 0.08). Incidence of AKI was 56.9% in the two-dose group versus 39.0% in the single-dose group (p = 0.01). There was no difference in bacterial (p = 0.40), fungal (p = 0.59), or viral (p = 0.78) infections. Acute cellular rejection through 6 months post-transplant was noted in 9.7% of patients receiving two doses and 6.3% in the single-dose arm (p = 0.42). Basiliximab-related cost savings in the single-dose arm was ∼$697 863.72 over 159 transplants. Single-dose basiliximab appears to be safe and effective in place of two doses in LDLTR with stable renal function on post-transplant Day 5. Utilization of a single basiliximab dose significantly reduced medication-related costs.

Single-dose versus multiple-dose antibiotics prophylaxis for preventing caesarean section postpartum infections: A randomized controlled trial.

Background:Caesarean section, a common obstetric surgical procedure, is a major predisposing factor for puerperal infections, requiring the need for antibiotic prophylaxis. Evidence suggests that single-dose antibiotic prophylaxis has comparable efficacy to multiple-dose antibiotic prophylaxis, but with a lower cost and risk of antibiotic resistance. However, single-dose antibiotic prophylaxis after caesarean section is not generally used in many centres in sub-Saharan Africa.Objective:This study aimed to compare the effectiveness of single- versus multiple-dose antibiotic prophylaxis to prevent post-caesarean section infections.Methodology:This open-label, randomized controlled trial involved 162 consenting patients admitted for caesarean section (elective or emergency) at the Federal Medical Centre Keffi. They were distributed randomly into treatment arm A or B. Subjects in both arms received intravenous ceftriaxone (1 g) and metronidazole (500 mg) 30–60 min before incision; subjects in arm B received additional parenteral doses for 48 h and then cefuroxime 500 mg tablets every 12 h and metronidazole 400 mg tablets every 8 h for 5 days. The patients were monitored for 2 weeks for evidence of wound infection, febrile morbidity and clinical endometritis.Result:There was no statistical difference in the incidence of wound infection (6.6% versus 7.4%; p = .882) and febrile morbidity (11.8% versus 11.1%, p = .807). However, clinical endometritis (0.0% versus 6.1%, p = .028) was statistically significant with none reported in the single-dose arm.Conclusion:Single-dose ceftriaxone and metronidazole is as effective as multiple doses for antibiotic prophylaxis to prevent post-caesarean section infections. Adoption of this approach in low-risk patients would reduce the cost of prophylactic antibiotics, workload for staff and antibiotic resistance.

Safety of Dalbavancin in the Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI): Nephrotoxicity Rates Compared with Vancomycin: A Post Hoc Analysis of Three Clinical Trials.

IntroductionDalbavancin is a lipoglycopeptide antibiotic approved as a single- and two-dose regimen for adults with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible gram-positive organisms. We present nephrotoxicity rates for patients with ABSSSI who received dalbavancin in three pivotal clinical trials and compare the rates with vancomycin.MethodsIn a phase 3b clinical trial (DUR001-303), patients were randomized to dalbavancin single-dose (1500 mg intravenous [IV]) or two-dose regimen (1000 mg IV on day 1, 500 mg IV on day 8). In two phase 3 clinical trials (DISCOVER 1 and DISCOVER 2), patients were randomized to dalbavancin (two-dose regimen) or vancomycin 1 g (or 15 mg/kg) IV every 12 h for at least 3 days with an option to switch to orally administered linezolid 600 mg every 12 h for 10–14 days. Patients on dalbavancin with a creatinine clearance below 30 mL/min not on regular dialysis received a reduced dose of 1000 mg (single-dose arm) or 750 mg IV on day 1, 375 mg IV on day 8 (two-dose arm). Nephrotoxicity was defined as a 50% increase from baseline serum creatinine (SCr) or an absolute increase in SCr of 0.5 mg/dL at any time point. P values were obtained using the Cochran–Mantel–Haenszel test.ResultsIn dalbavancin-treated patients, rates of nephrotoxicity were low. The safety population with available creatinine values included 1325/1347 patients on any regimen of dalbavancin, and 54/651 patients who received vancomycin intravenously for at least 10 days and were not switched to orally administered linezolid. Patients on any regimen of dalbavancin had a lower rate of nephrotoxicity compared with patients receiving vancomycin intravenously for at least 10 days (3.7% vs 9.3%, respectively; P = 0.039).ConclusionsNephrotoxicity rates were lower in patients on dalbavancin relative to vancomycin for at least 10 days. On the basis of this experience, dalbavancin may be less nephrotoxic than intravenously administered vancomycin.

Padsevonil randomized Phase IIa trial in treatment-resistant focal epilepsy: a translational approach.

Therapeutic options for patients with treatment-resistant epilepsy represent an important unmet need. Addressing this unmet need was the main factor driving the drug discovery program that led to the synthesis of padsevonil, a first-in-class antiepileptic drug candidate that interacts with two therapeutic targets: synaptic vesicle protein 2 and GABAA receptors. Two PET imaging studies were conducted in healthy volunteers to identify optimal padsevonil target occupancy corresponding to levels associated with effective antiseizure activity in rodent models. Optimal padsevonil occupancy associated with non-clinical efficacy was translatable to humans for both molecular targets: high (>90%), sustained synaptic vesicle protein 2A occupancy and 10–15% transient GABAA receptor occupancy. Rational dose selection enabled clinical evaluation of padsevonil in a Phase IIa proof-of-concept trial (NCT02495844), with a single-dose arm (400 mg bid). Adults with highly treatment-resistant epilepsy, who were experiencing ≥4 focal seizures/week, and had failed to respond to ≥4 antiepileptic drugs, were randomized to receive placebo or padsevonil as add-on to their stable regimen. After a 3-week inpatient double-blind period, all patients received padsevonil during an 8-week outpatient open-label period. The primary endpoint was ≥75% reduction in seizure frequency. Of 55 patients randomized, 50 completed the trial (placebo n = 26; padsevonil n = 24). Their median age was 36 years (range 18–60), and they had been living with epilepsy for an average of 25 years. They were experiencing a median of 10 seizures/week and 75% had failed ≥8 antiepileptic drugs. At the end of the inpatient period, 30.8% of patients on padsevonil and 11.1% on placebo were ≥75% responders (odds ratio 4.14; P = 0.067). Reduction in median weekly seizure frequency was 53.7% and 12.5% with padsevonil and placebo, respectively (unadjusted P = 0.026). At the end of the outpatient period, 31.4% were ≥75% responders and reduction in median seizure frequency was 55.2% (all patients). During the inpatient period, 63.0% of patients on placebo and 85.7% on padsevonil reported treatment-emergent adverse events. Overall, 50 (90.9%) patients who received padsevonil reported treatment-emergent adverse events, most frequently somnolence (45.5%), dizziness (43.6%) and headache (25.5%); only one patient discontinued due to a treatment-emergent adverse event. Padsevonil was associated with a favourable safety profile and displayed clinically meaningful efficacy in patients with treatment-resistant epilepsy. The novel translational approach and the innovative proof-of-concept trial design maximized signal detection in a small patient population in a short duration, expediting antiepileptic drug development for the population with the greatest unmet need in epilepsy.

Efficacy of a single dose versus a multiple dose regimen of Mebendazole against hookworm infections among school children: a randomized open-label trial

BackgroundDespite the existence of a population-based control program using single dose albendazole or mebendazole as a preventive chemotherapy, hookworm transmission remains high. It causes a negative impact on the growth and school performance of children. In connection to this preventive chemotherapy, different studies produced conflicting results. This study aimed at evaluating the efficacy of single (500 mg) versus multiple doses (100 mg twice a day during three consecutive days) of mebendazole against hookworm infections among school-aged children.MethodsThis randomized open-label clinical trial took place among school-aged children (6–14 years old) in Burie and Debre Elias towns, Northwest Ethiopia. Using simple randomization, eligible hookworm-positive children were allocated (1:1) to either a single or multiple dose treatment arms. Stool samples were collected and processed using McMaster method at baseline and follow-up period (14–21 days after treatment). Only laboratory technicians were blinded. The cure and egg reduction rates were the primary and secondary therapeutic outcome measures against hookworm infections, respectively. An independent t-test was used to compare group means, and logistic regression was used to calculate odds ratio (OR). P-value < 0.05 at 95% CI was considered statistically significant.ResultOne hundred eight children, 54 in each treatment arm had completed baseline data and received allocated treatment. One hundred three children had completed follow-up data records and included for the final efficacy analysis. Cure rate against hookworm was significantly higher in the multiple dose (96.1%) than in the single dose (30.8%) with OR = 55.125; 95% CI: 11.92–254.9; P < 0.001. The egg reduction rate in the multiple dose treatment arm (99.5%) was also significantly higher than in the single dose arm (68.9%) with difference t (101) =5.38; 95% CI 230.95–505.36; P < 0.001.ConclusionThe single dose regimen of mebendazole for the treatment of hookworm infections showed poor cure and egg reduction rates, while the multiple doses revealed satisfactory. Although multiple dose regimen administration is a bit more complex than the single dose, we strongly encourage replacing it with multiple dose regimen during deworming programs in hookworm endemic areas.Trial registrationThis trial is retrospectively registered in www.pactr.org, number PACTR201911466695052 on November 26, 2019.

Pharmacokinetics of Sativex® in Dogs: Towards a Potential Cannabinoid-Based Therapy for Canine Disorders.

The phytocannabinoid-based medicine Sativex® is currently marketed for the treatment of spasticity and pain in multiple sclerosis patients and is being investigated for other central and peripheral pathological conditions. It may also serve in Veterinary Medicine for the treatment of domestic animals, in particular for dogs affected by different pathologies, including human-like pathological conditions. With the purpose of assessing different dosing paradigms for using Sativex in Veterinary Medicine, we investigated its pharmacokinetics when administered to naïve dogs via sublingual delivery. In the single dose arm of the study, adult Beagle dogs were treated with 3 consecutive sprays of Sativex, and blood samples were collected at 12 intervals up to 24 h later. In the multiple dose arm of the study, Beagle dogs received 3 sprays daily for 14 days, and blood samples were collected for 24 h post final dose. Blood was used to obtain plasma samples and to determine the levels of cannabidiol (CBD), Δ9-tetrahydrocannabinol (Δ9-THC) and its metabolite 11-hydroxy-Δ9-THC. Maximal plasma concentrations of both Δ9-THC (Cmax = 18.5 ng/mL) and CBD (Cmax = 10.5 ng/mL) were achieved 2 h after administration in the single dose condition and at 1 h in the multiple dose treatment (Δ9-THC: Cmax = 24.5 ng/mL; CBD: Cmax = 15.2 ng/mL). 11-hydroxy-Δ9-THC, which is mainly formed in the liver from Δ9-THC, was almost undetected, which is consistent with the use of sublingual delivery. A potential progressive accumulation of both CBD and Δ9-THC was detected following repeated exposure, with maximum plasma concentrations for both cannabinoids being achieved following multiple dose. Neurological status, body temperature, respiratory rate and some hemodynamic parameters were also recorded in both conditions, but in general, no changes were observed. In conclusion, this study demonstrates that single or multiple dose sublingual administration of Sativex to naïve dogs results in the expected pharmacokinetic profile, with maximal levels of phytocannabinoids detected at 1–2 h and suggested progressive accumulation after the multiple dose treatment.

SAT-429 Final Results from the First in Man Phase 1 Clinical Trial of CRN00808, an Orally Bioavailable sst2-Selective, Nonpeptide Somatostatin Biased Agonist, for the Treatment of Acromegaly: Safety, Pharmacokinetics, Pharmacodynamics, and Midazolam Drug Interaction in Healthy Volunteers

Injected depot formulations of somatostatin peptide analogs are routinely used to treat acromegaly and neuroendocrine tumors (NETs). CRN00808 is a small molecule nonpeptide selective somatostatin receptor 2 agonist whose safety, pharmacokinetics (PK), and pharmacodynamics (PD) has been characterized in preclinical studies. This study describes the final results from a first-in-human, single and multiple ascending dose Phase 1 study in healthy volunteers to measure the safety, PK, PD, and midazolam drug interaction potential of CRN00808 (NCT03276858; preliminary results with blinded safety data presented at ENDO 2018). In the single dose arm of the study, cohorts of 8 subjects (6 active: 2 placebo) received CRN00808 as an oral solution or capsules (1.25 mg to 60 mg, or placebo). The effect of food on CRN00808 PK was also evaluated. In the multiple dose arm, cohorts of 9 subjects (6 active: 3 placebo) received CRN00808 capsules once daily (5 mg to 30 mg, or placebo) for 7-10 days. In the drug-interaction arm, a single cohort of 8 subjects received 20 mg of CRN00808 for 7 days; midazolam PK was assessed before (Day -2) and after (Day 7) administration of CRN00808. Safety and PK were assessed in all phases of the study. Suppression of GHRH-induced GH secretion and suppression of serum IGF-1 were measured as PD endpoints in the single and multiple dose phases of the study, respectively. Once daily administration of 5-30 mg CRN00808 capsules exhibited dose-dependent increases in peak (Cmax) and total (AUC) plasma exposures. The apparent terminal elimination half-life was determined to be of 42-50 hours and steady state was achieved in 3-5 days. Capsules taken with a standard high fat, high calorie meal resulted in a markedly lower plasma CRN00808 AUC (83%). Oral administration of CRN00808 resulted in dose-dependent suppression of both GHRH stimulated GH and IGF-1 secretion; a single 10 mg dose was found to cause 91% suppression of GHRH-stimulated GH and 10 mg once per day for 10 days resulted in maximal suppression of serum IGF-1. Midazolam PK was unaffected by co-administration of 20 mg CRN00808, suggesting little or no risk of drug interaction with CYP3A4/5 substrates. Treatment emergent adverse events associated with CRN00808 were generally mild and transient, and consistent with those reported with other somatostatin agonists. In conclusion, results from this Phase I clinical trial in healthy volunteers support further clinical development of CRN00808 as a once-daily oral treatment of patients with acromegaly.

Efficacy and Safety of a Single Dose versus a Multiple Dose Regimen of Mebendazole against Hookworm Infections in Children: A Randomised, Double-blind Trial

BackgroundSingle-dose mebendazole is widely used in preventive chemotherapy against the soil-transmitted helminths (STHs) Ascaris lumbricoides, hookworm and Trichuris trichiura, yet it shows limited efficacy against hookworm and T. trichiura infections. The use of adapted treatment regimens might provide a strategy to control and eliminate STH infections in STH-persistent settings. We evaluated the safety and efficacy of the multiple dose mebendazole regimen (3 days 100 mg bid) versus a single dose of 500 mg mebendazole in a setting with high STH prevalence and high drug pressure. MethodsThis randomised, double-blind clinical trial took place in a primary school on Pemba Island, Tanzania, in school-aged children (6–12 years). Using a computer random number generator (block size 10), hookworm-positive children were randomly assigned (1:1) to either a single or multiple dose regimen of mebendazole by an independent statistician. Two stool samples were collected at baseline and follow-up (18 to 22 days after treatment) for Kato-Katz analysis. The primary outcome was cure rate (CR) against hookworm. Secondary outcomes were egg reduction rate (ERR) against hookworm, CRs and ERRs against A. lumbricoides and T. trichiura, and tolerability assessed 3, 24 and 48 h post-treatment. Participants, investigators, caregivers, outcome assessors and the trial statistician were blinded. This trial is registered with ClinicalTrials.gov, number NCT03245398. Findings93 children were assigned to each treatment arm. 185 children completed treatment and provided follow-up stool samples. CR against hookworm was significantly higher in the multiple dose (98%) than in the single dose arm (13%, OR 389.1, 95% CI 95.2 to 2885.7%, p < 0.001). 34 and 42 children reported mild adverse events in the single and multiple dose arms, respectively. The most common events were abdominal pain, headache and diarrhoea. InterpretationThe poor performance of single dose mebendazole against hookworm infections was confirmed, but the multiple dose treatment regimen of mebendazole showed high efficacy. Hence, multiple dose mebendazole might provide a treatment strategy in given epidemiological situations to boost control and elimination of STH infections. FundingPATH.

Single dose ceftriaxone and metronidazole versus multiple doses for antibiotic prophylaxis at elective caesarean section in Mulago hospital: A randomized clinical trial

Objective: To compare the incidence of post-operative infections among mothers who received single dose pre-operative ceftriaxone and metronidazole compared to multiple doses after delivery by elective caesarean section. Methods: This was (parallel, balanced randomization, 1:1) open label randomized controlled trial conducted Mulago Hospital, Department of Obstetrics and Gynaecology. Participants included in this study were pregnant women who had been admitted for elective caesarean section. The mothers were randomized to receive single dose of ceftriaxone and metronidazole minutes before the operation or multiple doses 30-60 during the operation and postoperatively. The primary outcome was post-operative wound infection. Secondary outcomes were clinical endometritis and febrile morbidity. The 174 eligible participants were randomized into one of the two treatment arms in a ratio of 1:1. The research assistants who collected the outcomes were blinded to the study allocation. Results: Of the 174 eligible participants who recruited; 87 were randomized to the single dose group while 87 to the multiple doses group. The participants were recruited from 17th September 2015 up to 29th February 2016. All the participants were followed up for two weeks after delivery. Outcome data was available for 79 women in the single dose group and 81 women in the multiple dose group. There were no differences in the incidence of post-operative wound infections between the single dose arm versus the multiple dose arm (RR 1.895; 95% CI (0.2-21.4). There was no clinical endometritis and febrile morbidity observed during the 14 days of follow up. Conclusion: Single dose pre-operative antibiotic prophylactic with ceftriaxone and metronidazole is as effective as multiple doses in prevention of post-operative infectious morbidity in women who undergo elective caesarean section. We recommend the use of single dose ceftriaxone and metronidazole in women undergoing elective caesarean section in our setting. Trial registration: NCT02736682. Registration date, 7th April, 2016.

Exploratory Pharmacokinetic/Pharmacodynamic and Tolerability Study of BCMAxCD3 in Cynomolgus Monkeys

JNJ-64007957 is a bispecific antibody that binds to CD3 on T cells, and BCMA on plasma cells, and should induce T cell mediated killing of BCMA expressing malignant plasma cells.The objectives of this study were to characterize the tolerability of JNJ-64007957 when given intravenously as either single- or repeated-doses (5 total doses) to male cynomolgus monkeys. Pharmacokinetics (PK) and pharmacodynamics (PD) were evaluated in the repeat-dose groups; the single dose arms allowed for PK evaluations through Day 56, and determination of key PK parameters to support FIH dose modeling.Methods:The cynomolgus monkey was chosen for this study as JNJ-64007957 binds to both cynomolgus monkey CD3 and BCMA and it is an accepted non-rodent species for nonclinical tolerability, PK and PD evaluations. In this study, male monkeys (3/group) were administered either control or JNJ-64007957 via slow intravenous bolus injection on Days 1, 8, 15, 22, and 29 for repeat dose groups (1-4) and on Day 1 for single dose groups (5-6). The JNJ-64007957 doses were 0, 0.1, 1 and 10 mg/kg/week for repeat dose administration, and 1 or 10 mg/kg for single dose administration. Monkeys were evaluated for general tolerability, and samples were collected for PK and PD evaluations.Results:JNJ-64007959 was well tolerated upto 10 mg/kg. PK assessments showed that Cmax and AUC increased in a dose proportional manner, and the overall PK profiles suggested very low anti-drug antibody responses. For repeat dose groups, accumulation ratio was approximately 2. This supports dosing frequency of more than one week.There were no toxicologically significant findings in the monkeys at doses up to 10 mg/kg/week. Some minor changes in lymphoid cellularity were noted including an apparent slight to minimal and non-dose dependent decreases in plasma cells within one or more of the lymphoid tissues. There were no changes in peripheral blood lymphocytes or cytokine release. The small number of animals in this study precludes making definitive conclusions regarding the pharmacodynamics effects of dual BCMA and CD3 engagement but this will be investigated in a larger study that will support first in human dosing.Conclusions:Overall, this exploratory cynomolgus monkey study was designed to evaluate JNJ-64007957 tolerability and PK/PD in one study. This study indicated that a BCMAxCD3 bispecific antibody showed no toxicologically significant effects when administered to monkeys once per week for 5-weeks and exposure was dose proportional. DisclosuresGirgis:Janssen Research & Development: Employment. Shetty:Janssen Research & Development: Employment. Jiao:Janssen Research & Development: Employment. Amuzie:Janssen Research & Development: Employment. Weinstock:Janssen Research & Development: Employment. Grimme Watson:Janssen Research & Development: Employment. Ford:Janssen Research & Development: Employment. Pillarisetti:Janssen: Employment. Baldwin:Janssen: Employment. Bellew:Janssen: Employment.

Raising expectations for subunit vaccine.

Multidose regimens are recommended for all prophylactic subunit vaccines. Recent findings from clinical trials of an human papillomavirus virus-like particle vaccine suggest that it may be possible to develop effective single-dose subunit vaccines. The broad implications of these findings are discussed, and the importance of antigen structure and adjuvant in achieving this goal is considered. In conclusion, we argue for the inclusion of single-dose arms in future trials of vaccines, especially if they are based on induction of antibodies by virus-like displayed antigens.

The influence of ART on the treatment of Trichomonas vaginalis among HIV-infected women.

Among women who are human immunodeficiency virus positive (HIV+), both prevalent and persistent infections with Trichomonas vaginalis (TV) are common. TV has been shown to increase vaginal shedding of HIV, which may influence HIV sexual and perinatal transmission, making prevention important. In 1 cohort of HIV+ women in Kenya, antiretroviral therapy (ART) use, mostly nevirapine based, was associated with lower cure rates of TV for single-dose therapy. Our goal was to repeat this study in a US-based cohort of HIV+/TV+ women and compare outcomes to those with multidose therapy. A secondary data analysis was performed on a multicentered cohort of HIV+/TV+ women who were randomized to single-dose (2 grams) or 7-day (500 mg twice daily) multidose metronidazole (MTZ) treatment. Test of cure visit, via culture, occurred 6-12 days after treatment completion. Information was collected on sex partner treatment and sexual exposures. Persistent TV infection rates were compared for women on ART at baseline vs not on ART. Of the 226 women included, those on ART had more treatment failures than women not on ART (24/146 [16.4%] vs 5/80 [6.3%]; P = .03). When stratified by treatment arm, more treatment failures were seen in the single-dose arm (17/73 [23.3%] vs 3/39 [7.7%]; P = .05) than in the multidose arm (7/73 [9.6%] vs 2/41 [4.8%]; P = .39). ART usage was associated with a higher TV persistent infection rate among those receiving the single-dose treatment, but not the multidose, providing more evidence that multidose should be the preferred treatment for HIV+ women.

P2.102 The Influence of Anti Retroviral Treatment (ART) on the Treatment of Trichomonas Vaginalis Among HIV-Infected Women in Three Southern Cities the U.S.

BackgroundTrichomonas vaginalis (TV) is the most common non-viral STI and has been linked to premature membrane rupture, preterm birth, and low birth weight in pregnant women. TV has also been...

Comparative efficacy of one versus two doses of praziquantel on cure rate of Schistosoma mansoni infection and re-infection in Mayuge District, Uganda

The current recommended control strategy for schistosomiasis is annual treatment using 40 mg/kg of praziquantel. However, praziquantel is only effective on adult worms and giving a second dose may increase its efficacy. We assessed the effect of one versus two doses of praziquantel on cure rate and re-infection with Schistosoma mansoni in a high endemic community along Lake Victoria, Uganda. To investigate the effect of the two regimens, 395 infected people were randomised into two groups; one received a single standard dose of praziquantel (Distocide® 600 mg, Shin Poong Pharmaceuticals, Seoul, Republic of Korea), 40mg/kg body weight, while the other group received a second dose 2 weeks later. Cure rate and infection intensity were assessed 9 weeks after the first treatment using standard parasitological procedures. Re-infection levels were monitored 8 and 24 months after treatment. Those who received two doses were more likely to be cured (69.7%) compared to those who received a single dose (47.9%) (χ(2) = 18.5, p < 0.001). Geometric mean intensity (GMI) of infection at 9 weeks (eggs per gram of faeces [epg]) was 12.0 epg (CI95: 8.9-16.1) for individuals who received 2 doses and 22.1 epg (CI95: 16.9-28.8) for those in the single dose arm. Eight months after treatment, prevalence of re-infection for individuals in the double dose arm (61.6%, CI95: 50.2-73.1) was not significantly different from that of those in a single dose arm (68.3%, CI95: 59.9-76.8). The difference in GMI of re-infection for individuals in the single dose arm (33.8 epg, CI95: 23.2-49.3) and those in the double dose arm (34.5 epg, CI95: 24.7-48.1) was not significant. Twenty four months after treatment, prevalence of re-infection was not significantly different. The difference in GMI of re-infection for those in the single dose arm (57.5 epg, CI95: 33.9-97.5) and those in the double dose arm (42.2 epg, CI95: 29.9-59.6) was also insignificant. Our results suggest that a second dose of praziquantel given 2 weeks after the first dose improves cure rate and reduces S. mansoni infection intensity. However, there is no added advantage on reduction of S. mansoni re-infection by administering two doses of praziquantel. CLINICAL TRIALS.GOV IDENTIFIER: NCT00215267.

A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome

Tumor lysis syndrome (TLS) is a life-threatening disorder characterized by hyperuricemia and metabolic derangements. The efficacy of rasburicase, administered daily for 5 days, has been well established. However, the optimal duration of therapy is unknown in adults. We evaluated the efficacy of rasburicase (0.15 mg/kg) administered as single dose followed by as needed dosing (maximum five doses) versus daily dosing for 5 days in adult patients at risk for TLS. Eighty of the 82 patients enrolled received rasburicase; 40 high risk [median uric acid (UA) 8.5 mg/dl; range, 1.5-19.7] and 40 potential risk (UA = 5.6 mg/dl; range, 2.4-7.4). Seventy-nine patients (99%) experienced normalization in their UA within 4 h after the first dose; 84% to an undetectable level (<0.7 mg/dl). Thirty-nine of 40 (98%) patients in the daily-dose arm and 34 of 40 (85%) patients in single-dose arm showed sustained UA response. Six high-risk patients within the single-dose arm required second dose for UA >7.5 mg/dl. Rasburicase was well tolerated; one patient with glucose-6-phosphate dehydrogenase deficiency developed methemoglobinemia and hemolysis. Rasburicase is highly effective for prevention and management of hyperuricemia in adults at risk for TLS. Single-dose rasburicase was effective in most patients; only a subset of high-risk patients required a second dose.

Prophylaxis of Acute Gvhd Using Stromal Cell Therapy: Preliminary Results After Administration of Single or Multiple Doses of Multistem® in a Phase I Trial

Abstract 1987 Background.MultiStem®, a multipotent adult progenitor cells (MAPC) collection, is an immune-modulatory, bone marrow-derived adult adherent allogeneic stromal cell product manufactured to large scale, assuring consistency of universal donor cell product during clinical evaluation. Pre-clinical studies showed safety of IV infusion and survival benefit in a haploidentical transplantation rat model of acute GVHD (Kovacsovics 2008, 2009). Methods.An open label Phase I clinical dose escalation study is being conducted with the primary goal to assess safety of MAPC as an adjunct treatment for human subjects undergoing myeloablative allogeneic HSCT for hematologic malignancies. Patients have been enrolled for MultiStem® administration as a single dose or in multiple weekly doses. Infusional toxicity and RRTs are assessed for 30 days following the last study drug dose administration. Secondary endpoints include incidence of acute GVHD, infection and survival through day 100. Dose escalation is guided by the Continual Reassessment Method (CRM). Results.In the single dose arm, 18 patients with AML (9), MDS (4), CML (3) and ALL (2) from 5 clinical centers were administered MultiStem® IV at 1, 5, or 10 million cells per kg at day 2 after allogeneic HSCT. There was no observed infusional toxicity. Two patients experienced Bearman RRTs (Gr 3 mucositis; Gr 3 renal & pulmonary failure) deemed unrelated to study product. Engraftment occurred in all 18 patients. The median time to neutrophil engraftment for related (n=7) and unrelated (n=11) HSCT was 15 days (range, 12–16 days) and 14 days (range, 11–25 days), respectively. The 100-day cumulative incidence of Grade II-IV and III-IV GVHD was 28% and 6% (n=18). In the highest MultiStem® dose group (n=9) there was no grade III-IV GVHD, and only one case of grade II GVHD, which subsequently resolved with treatment. 17/18 patients have been enrolled in the multidose arm. Results of safety endpoints and interim results of all secondary endpoints of repeated MultiStem® administrations following HSCT will be presented. Conclusion.Single dose administration of MultiStem® is well-tolerated, without observation of infusional toxicity or graft failure. Together with the observed low incidence of severe aGVHD, these findings are supportive of the concept that stromal stem cell therapy is safe and may be harnessed as an efficacious therapeutic option for acute GVHD prophylaxis following HSCT. [Display omitted] Disclosures:Maziarz:Athersys, Inc: Patents & Royalties, Research Funding. Perry:Athersys, Inc.: Employment. Deans:Athersys, Inc: Employment. Van’t Hof:Athersys, Inc.: Employment.

Single-dose liposomal amphotericin B (AmBisome®) for the treatment of visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial.

BackgroundAmBisome® is an efficacious, safe anti-leishmanial treatment. There is growing interest in its use, either as a single dose or in combination treatments. In East Africa, the minimum optimal single-dosage has not been identified.Methods/DesignAn open-label, 2-arm, non-inferiority, multi-centre randomised controlled trial is being conducted to determine the optimal single-dose treatment with AmBisome®.Patients in the single-dose arm will receive one infusion on day 1, at a dose depending on body weight. For the first group of patients entered to the trial, the dose will be 7.5 mg/kg, but if this dose is found to be ineffective then in subsequent patient series the dose will be escalated progressively to 10, 12.5 and 15 mg/kg. Patients in the reference arm will receive a multi-dose regimen of AmBisome® (3 mg/kg/day on days 1-5, 14 and 21: total dose 21 mg/kg). Patients will be hospitalised for approximately one month after the start of treatment and then followed up at three and six months. The primary endpoint is the status of patients six months after treatment. A secondary endpoint is assessment at day 30. Treatment success is determined as the absence of parasites on microscopy samples taken from bone marrow, lymph node or splenic aspirates. Interim analyses to assess the comparative efficacy of the single dose are planned after recruitment of 20 and 40 patients per arm. The final non-inferiority analysis will include 120 patients per arm, to determine if the single-dose efficacy 6 months after treatment is not more than 10% inferior to the multi-dose.DiscussionAn effective, safe single-dose treatment would reduce hospitalization and treatment costs. Results will inform the design of combination treatment studies.Trial RegistrationClinicalTrials.gov NCT00832208

The influence of bacterial vaginosis on the response to Trichomonas vaginalis treatment among HIV-infected women

ObjectiveTrichomonas vaginalis (TV) is common in HIV+ women, and host factors may play a role in TV treatment outcomes. The purpose of this study was to examine the influence of...

One preoperative dose randomized against 3‐day antibiotic prophylaxis for transrectal ultrasonography‐guided prostate biopsy

To compare the incidence of infective events between a single dose and 3-day antibiotic prophylaxis for transrectal ultrasonography (TRUS)-guided prostate biopsy. Patients were randomized to receive either one preoperative dose consisting of two ciprofloxacin 500 mg tablets 2 h before prostate biopsy, or 3 days of ciprofloxacin treatment. They had a clinical examination at study inclusion, the day of the biopsy and 3 weeks later. The day after the procedure all patients were contacted by telephone to inquire about any significant event. Biological testing and urine cultures were conducted 5 days before and then 5 and 15 days after the biopsy; a self-administered symptom questionnaire was completed by the patient 5 days before and then at 5 and 15 days. The study group included 288 men, of whom 139 were randomized to the single-dose arm and 149 to the 3-day arm. Six patients in each group had an asymptomatic bacteriuria with no leukocyturia. One patient in each group had documented prostatitis, with Escherichia coli identified on urine culture. The strain identified in the patient from the 3-day group was resistant to ciprofloxacin. There was no difference between groups in symptoms at 5 and 21 days after biopsy. Current TRUS-guided prostate biopsy techniques lead to very few clinical infectious complications when accompanied by antibiotic prophylaxis. We found no argument to advocate the use of more than one dose of antibiotic prophylaxis.

Randomized trial in multiparous patients: investigating a single vs. two-dose regimen of intravaginal misoprostol for induction of labor

Background. Multiparous patients have a higher risk of hyperstimulation and uterine rupture than nulliparous patients. The minimum possible dose of uterotonic drug should be used in induction of labor for multiparous patients to avoid excessive uterine activity, which could increase both maternal and fetal risks. Methods. One hundred and four women were randomized to either a single dose of 50 µg of intravaginal misoprostol in 24 h, or two consecutive doses of intravaginal 50 µg misoprostol 6 h apart. Results. The mean induction to delivery interval (789 min [95% CI: 637–941] vs. 576 min [95% CI: 484–667], p = 0.018) and delivery rate within 12 h (63% vs. 83%, p = 0.035) were higher in the two-dose group. The oxytocin augmentation rate (14% vs. 2%, p = 0.03) was higher in the single-dose group. There was a higher rate of clinician input related to suspicious cardiotocographic readings in the single-dose arm ( p = 0.04). There was no statistical difference ( p > 0.05) between the one- and two-dose regimens with respect to the rates of tachysystole (21% vs. 15%), hyperstimulation (3.9% vs. 0%), and meconium staining at delivery (9.8% vs. 13.2%). Conclusions. The two-dose regimen was most efficient, but both regimens were well tolerated by the fetuses.