Intravenous Infusion In Patients Research Articles

Pharmacokinetics (PK) of Tiragolumab in First-in-Human Study in Patients with Mixed Solid Tumors (GO30103).

Tiragolumab is a first-in-class, fully human IgG1/kappa anti-TIGIT monoclonal antibody that blocks the binding of TIGIT to CD155 (the poliovirus receptor). We summarize the pharmacokinetics (PK) data from the phase1a/1b GO30103 study of Q3W (every 3weeks) sequential dosing of tiragolumab (2, 8, 30, 100, 400, 600, or 1200mg) followed by atezolizumab (1200mg), Q4W (every 4weeks) sequential dosing (tiragolumab 840mg followed by atezolizumab 1680mg), and Q4W co-infusion (tiragolumab 840mg plus atezolizumab 1680mg). Serum samples were collected at multiple time points following tiragolumab and atezolizumab intravenous infusion in patients with solid tumors for PK and immunogenicity assessment. The serum PK profile of tiragolumab appeared to be biphasic, with a rapid distribution phase followed by a slower elimination phase when administered alone or in combination with atezolizumab. In phase1a, across doses of tiragolumab ranging from 2 to 1200mg (cycle1), the geometric mean (GM), coefficient of variation (CV%), serum tiragolumab Cmax ranged from 0.682 to 270µg/mL (18.6% to 36.5%) and Cmin ranged from 0.0125 to 75.3µg/mL (0.0% to 24.2%). The GM systemic exposure (area under the plasma drug concentration-time curve, AUC0-21) ranged from 310 to 2670µgday/mL (20.5% to 27.0%); interindividual variability in AUC0-21 ranged from 20.5% to 43.9%. Tiragolumab exposure increased in an approximately dose-proportional manner when administered alone or with atezolizumab at doses ≥100mg. Postbaseline, 4/207 patients (1.9%) were positive for treatment-emergent antidrug antibodies (ADA) against tiragolumab, each at a single time point. Tiragolumab combined with atezolizumab demonstrated desirable PK properties, with no drug-drug interactions or immunogenicity liability. There were no meaningful differences in tiragolumab or atezolizumab exposure between the Q4W co-infusion and sequential dosing cohorts. ClinicalTrials.gov: NCT02794571 (date of registration June 6, 2016).

Efficacy of Systematic Nursing Combined with Lianzhi Xiaoyan Capsule on Clinical Outcome of Emergency Intravenous Infusion in Patients with Acute Gastroenteritis

This study aimed to explore the efficacy of systematic nursing combined with Lianzhi Xiaoyan capsule on clinical efficacy and the incidence of adverse reactions due to emergency intravenous infusion in patients with acute gastroenteritis. The patients were divided into a control group, comprising patients who received conventional Western medicine treatment and routine emergency nursing, and an observation group, comprising patients who received conventional Western medicine treatment and routine emergency nursing combined with Lianzhi Xiaoyan capsules. The total effective rates among patients in the observation group were higher than those among patients in the control group (P < 0.05). The durations of fever, abdominal pain, diarrhea, nausea, and vomiting among patients in the observation group were shorter than those among patients in the control group. High-sensitivity C-reactive protein, interleukin-6, and CD8+ levels among patients in the observation group were lower than those among patients in the control group. The incidences of adverse reactions during intravenous infusion were lower, and patient satisfaction with nursing care was higher among patients in the observation group than among those in the control group. Systematic nursing combined with Lianzhi Xiaoyan capsules has significant clinical efficacy and can reduce emergency intravenous infusion-related adverse reactions in patients with acute gastroenteritis.

Meta-pharmacokinetic analysis of posaconazole following dosing of oral suspension, delayed-release tablet, and intravenous infusion in patients vs. healthy volunteers: Impact of clinical characteristics and race

ObjectivesTo investigate the potential impact of clinical characteristics and the Chinese race on posaconazole pharmacokinetics in patients using an integrated population pharmacokinetic model for posaconazole oral suspension (SUS), delayed-release tablet (DR-tablet), and intravenous (IV) infusion that was developed in healthy volunteers (HV). Methods1046 concentrations from 105 prospectively studied Caucasian patients receiving either of the three posaconazole formulations were pooled with 3898 concentrations from 182 HV. Clinical characteristics were tested for significance. The impact of Chinese race was assessed using 292 opportunistic samples from 80 Chinese patients receiving SUS. ResultsBioavailability of SUS (Fsus) in patients decreased from 38.2% to 24.6% when the dose was increased from 100 mg to 600 mg. Bioavailability of DR-tablet (Ftab) was 59% regardless of dose. Mucositis, diarrhoea, administration through a nasogastric tube, and concomitant use of proton pump inhibitors or metoclopramide reduced Fsus by 61%, 36%, 44%, 48%, and 29%, respectively, putting patients with these characteristics at increased risk of inadequate exposure. Clearance decreased from 7.0 to 5.1 L/h once albumin levels were <30 g/L. Patients showed an 84.4% larger peripheral volume of distribution (Vp) and 67.5% lower intercompartmental clearance (Q) compared with HV. No racial difference could be identified. ConclusionsPharmacokinetics of posaconazole in patients differ considerably to those in HV, with altered Fsus that is also impacted by clinical covariates, an Ftab similar to fasted conditions in HV, and altered parameters for clearance, Vp, and Q. There was no evidence to indicate that Chinese patients require a different dose to Caucasian patients.

A phase 1, first-in-human, open label, escalation and expansion study of ORM-5029, a highly potent GSPT1 degrader targeting HER2, in patients with HER2-expressing advanced solid tumors.

TPS1114 Background: Targeted protein degradation (TPD) molecules have expanded the therapeutic options through their catalytic mechanism of action (MOA) and ability to degrade “undruggable” proteins. To increase the efficacy versus tolerability window of protein degradation and improve drug delivery, ORM-5029 uses a Dual-Precision TPD (TPD2) approach combining the catalytic mechanism of TPDs with the precision of tumor-targeting therapeutic antibodies. ORM-5029 is a first-in-class human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate (ADC) comprised of SMol006, a highly potent GSPT1 degrader, conjugated to pertuzumab, a clinically validated antibody. HER2 is overexpressed in cancers such as breast, ovarian and gastric, and associated with early-onset aggressive disease. ORM-5029 is in development for treatment of HER2-expressing solid tumors. The MOA is mediated by targeted uptake of the ADC, release of the TPD payload, and cell death by GSPT1 degradation. ORM-5029 showed robust in vitro and in vivo efficacy in multiple HER2-expressing models with comparable activity to trastuzumab deruxtecan and strong activity in trastuzumab emtansine-refractory models. Methods: This phase 1 first-in-human study evaluates the safety, tolerability, and efficacy of ORM-5029 administered by intravenous infusion in patients (pts) with HER2-expressing advanced solid tumors (NCT05511844). The escalation, guided by the Bayesian Optimal Interval design, explores cohorts of ORM-5029 to identify the maximum tolerated dose (MTD) and/or expansion dose level (EDL). Each cohort will enroll ≥3 breast cancer pts with at least HER2 1+ (HER2 low) or greater by immunohistochemistry or positive by in situ hybridization. Expansion cohort A (HER2+ breast cancer) may enroll in parallel to escalation evaluating doses showing pharmacodynamic activity or efficacy. Up to 10 pts may be enrolled at each dose explored in cohort A. Enrollment into expansion cohort B (up to 21 pts) and cohort C (up to 22 pts) will begin once the EDL has been determined to further assess the safety, tolerability and efficacy of ORM-5029 using a Simon’s optimal 2-stage design. Cohort B will enroll pts with HER2+ breast cancer refractory or intolerant to standard treatment after ≥2 HER2 therapies in the metastatic setting. Cohort C will enroll pts with advanced solid tumors that are refractory or intolerable to standard treatment or for which no standard treatment is available, including HER2+ gastric or gastroesophageal junction adenocarcinoma or tumors with HER2 expression, amplification or mutations (e.g., colorectal, bile duct, ovarian, bladder, non-small cell lung). Study enrollment began in October 2022 in the United States. Escalation cohort 1 was completed without DLT; enrollment in cohort 2 began as of December 2022. Clinical trial information: NCT05511844 .

Corrigendum to “Safety, Tolerability, Pharmacokinetics, and Efficacy of Terlipressin Delivered by Continuous Intravenous Infusion in Patients with Cirrhosis and Refractory Ascites”

Corrigendum to “Safety, Tolerability, Pharmacokinetics, and Efficacy of Terlipressin Delivered by Continuous Intravenous Infusion in Patients with Cirrhosis and Refractory Ascites”

ATX-101, a cell-penetrating protein targeting PCNA, can be safely administered as intravenous infusion in patients and shows clinical activity in a Phase 1 study

Proliferating Cell Nuclear Antigen (PCNA) is a highly conserved protein essential for DNA replication, repair and scaffold functions in the cytosol. Specific inhibition of PCNA in cancer cells is an attractive anti-cancer strategy. ATX-101 is a first-in-class drug targeting PCNA, primarily in cellular stress regulation. Multiple in vivo and in vitro investigations demonstrated anti-cancer activity of ATX-101 in many tumor types and a potentiating effect on the activity of anti-cancer therapies. Healthy cells were less affected. Based on preclinical data, a clinical phase 1 study was initiated. Twenty-five patients with progressive, late-stage solid tumors were treated with weekly ATX-101 infusions at four dose levels (20, 30, 45, 60 mg/m2). ATX-101 showed a favorable safety profile supporting that vital cellular functions are not compromised in healthy cells. Mild and moderate infusion-related reactions were observed in 64% of patients. ATX-101 was quickly cleared from blood with elimination half-lives of less than 30 min at all dose levels, probably due to both, a quick cell penetration and peptide digestion in serum, as demonstrated in vivo. No tumor responses were observed but stable disease was seen in 70% of the efficacy population (n = 20). Further studies have been initiated to provide evidence of efficacy. Trial registration numbers: ANZCTR 375262 and ANZCTR 375319.

Efficacy of High-Dose Vitamin C Infusion on Outcomes in Sepsis Requiring Mechanical Ventilation: A Double-Blind Randomized Controlled Trial.

Background Critically ill patients have an increased requirement for vitamin C in sepsis and these patients have low levels of vitamin C. The researchers validated the efficacy of high-dose vitamin C intravenous infusion (IVI) in patients with sepsis requiring mechanical ventilation. Methods Forty patients were randomly assigned to 2 groups (20 each) in a 1 : 1 ratio in accordance with the vitamin C treatment regimen: Group I (GI): patients received 1.5 g/6 h vitamin C in 50 ml of dextrose 5% in water (D5W) IVI over 30 minutes for 4 consecutive days; Group II (GII): patients received 100 mg vitamin C/day as a first single dose in 50 ml of D5W IVI over 30 minutes and the other three subsequent doses were 50 ml of plain D5W IVI over 30 minutes for 4 consecutive days. Primary outcomes were the change in sequential organ failure assessment (SOFA) score at day 7, the incidence of ventilator-associated pneumonia (VAP), and the plasma vitamin C level. The glutathione peroxidase (GPX) activity, C-reactive protein (CRP) level, duration of vasopressor therapy, and 28-day mortality were secondary outcomes. Results The change in SOFA score at day 7 showed a significant difference between GI and GII (p < 0.001). The incidence of early VAP was significantly lower in GI (p=0.044). Vitamin C levels showed a significant rise in GI at day 1 and day 4 (p < 0.001 and p < 0.001, respectively). GPX activity of day 4 and day 7 was significantly higher in GI (p=0.005 and p=0.014, respectively). CRP levels of day 4 and day 7 were significantly higher in GII (p < 0.001 and p < 0.001, respectively). There was a significant difference in 28-day mortality (p=0.038) and duration of vasopressor therapy (p=0.033) in GI compared to GII. Conclusion The early use of high-dose vitamin C intravenous infusion in patients with sepsis requiring mechanical ventilation in combination with the standard treatment for sepsis lowered the incidence of VAP, increased the antioxidant status, and improved the illness severity. Trial Registration. This trial is registered with ClinicalTrials.gov Identifier (NCT04029675).

Safety, Tolerability, Pharmacokinetics, and Efficacy of Terlipressin Delivered by Continuous Intravenous Infusion in Patients with Cirrhosis and Refractory Ascites

Background. Terlipressin is a long acting synthetic analogue of vasopressin, which is used to manage variceal bleeding and hepatorenal syndrome. Terlipressin is being developed to treat refractory ascites in cirrhotic patients who are no longer responsive to diuretic drugs and require repeated paracentesis. This study evaluated the safety, tolerability, pharmacokinetics (PK), and efficacy of a continuous intravenous (IV) infusion of terlipressin as an outpatient treatment for refractory ascites in patients with advanced liver cirrhosis. Methods. This was an open-label Phase 2a trial. Patients received a continuous IV infusion of terlipressin 2 mg/day escalating to 4 mg/d during an initial 7-day inpatient period, followed by 21 days as outpatients. The PK, safety/tolerability, and effects on the need for and volume of paracentesis were evaluated. Results. Four of 6 patients experienced ≥50% increase in the interval between large volume paracenteses (LVP) with terlipressin. The volume of ascites removed by LVP in the 28-day treatment period was reduced in all patients by ≥30% compared with pretreatment. Terlipressin was rapidly eliminated with a mean half-life of 42.3 minutes, mean clearance of 5.6 mL/min/kg, and volume of distribution of 0.33 L/kg. Average steady state plasma concentrations ranged from 1.69 to 5.55 ng/mL and increased proportionally with increasing dose. Three (50.0%) patients reported treatment-related adverse events, but none were serious. Conclusion. Continuous terlipressin IV infusion improved control of refractory ascites with an acceptable safety and predictable PK profile. Further evaluation of terlipressin is warranted in a randomized controlled trial for treating refractory ascites and related complications of cirrhosis.

Safety, tolerability, pharmacokinetics and pharmacodynamic activity of terlipressin delivered by continuous intravenous infusion in patients with cirrhosis and refractory ascites: a phase 2a open-label trial

Safety, tolerability, pharmacokinetics and pharmacodynamic activity of terlipressin delivered by continuous intravenous infusion in patients with cirrhosis and refractory ascites: a phase 2a open-label trial

The Safety and Exploration of the Pharmacokinetics of Intrapleural Liposomal Curcumin.

BackgroundMalignant pleural effusion (MPE) is the accumulation of fluid in the pleural cavity as a result of malignancies affecting the lung, pleura and mediastinal lymph nodes. Curcumin, a compound found in turmeric, has anti-cancer properties that could not only treat MPE accumulation but also reduce cancer burden. To our knowledge, direct administration of curcumin into the pleural cavity has never been reported, neither in animals nor in humans.PurposeTo explore the compartmental distribution, targeted pharmacokinetics and the safety profile of liposomal curcumin following intrapleural and intravenous administration.MethodsLiposomal curcumin (16 mg/kg) was administered into Fischer 344 rats by either intrapleural injection or intravenous infusion. The concentration of curcumin in plasma and tissues (lung, liver and diaphragm) were measured using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Blood and tissues were examined for pathological changes.ResultsNo pleural or lung pathologies were observed following intrapleural liposomal curcumin administration. Total curcumin concentration peaked 1.5 hrs after the administration of intrapleural liposomal curcumin and red blood cell morphology appeared normal. A red blood cells abnormality (echinocytosis) was observed immediately and at 1.5 hrs after intravenous infusion of liposomal curcumin.ConclusionThese results indicate that liposomal curcumin is safe when administered directly into the pleural cavity and may represent a viable alternative to intravenous infusion in patients with pleural-based tumors.

Safety Profile of HTX-019 Administered as an Intravenous Infusion in Patients With Cancer: A Retrospective Analysis.

HTX-019 is a neurokinin 1 receptor antagonist approved for prevention of acute and delayed chemotherapy-induced nausea and vomiting in patients with cancer receiving moderately and highly emetogenic chemotherapy. When administered as a 30-minute intravenous (IV) infusion, HTX-019 has displayed a tolerable and favorable safety profile in healthy subjects. This is the first study to evaluate the safety profile of multiple HTX-019 infusions in patients with cancer. This retrospective analysis shows that HTX-019 administered via IV infusion has a favorable safety profile in patients with cancer, and no new treatment-emergent adverse events were identified.

Safety and efficiency of the port-catheter for intensive intravenous chemotherapy in patients with multi-drug resistant tuberculosis and extensively drug-resistant tuberculosis

PURPOSE. To study the efficacy and tolerability of the port catheter for continuous intravenous infusion in patients with MDR-TB and XDR-TB.&#x0D; MATERIALS AND METHODS. In a controlled study examined the effectiveness of the port catheter during an intensive 7-component anti-TB treatment with intravenous application of 3 anti-TB drugs (moxifloxacin, PAS, linezolid) in 16 patients with MDR-TB and XDR-TB. In the comparison group, which is formed by a pair of matching according to the drug resistance profile of MTB, the same intensive chemotherapy regimens in which the infusion of these drugs was carried out by daily injections of veins. In each group dominated patients with retreatment cases – 14 (87.5 %) patients. The planned duration of intravenous therapy was 2–4 months.&#x0D; RESULTS. Port-catheter for continuous infusion of combination of anti-tuberculosis drugs in comparison to their administration in the usual way ensures high efficiency and safety. In any case, was not observed phlebitis, no complaints of pain at the injection site, only 12.5 % cases were hematoma after setting the port in comparison to 100.0 % of patients with daily venous injections. In the study group was not a single case of interruption of intravenous infusion. In the control group, 56.2 % of patients discontinued intravenous treatment due to inability to penetrate the vein, patient’s complaints pain or phlebitis. At the end of the intensive phase of chemotherapy sputum conversion and disappearance of clinical symptoms were observed in 15 (3.7 %) patients of the study group, that was 26.7 % higher, than in control group (p&gt;0,05). We found significant difference in terms of sputum conversion, which occurred in the study group through (2,2±0,1) months vs (3,7±0,3) months (&lt;0,05) in control group.&#x0D; CONCLUSIONS. Port-catheter for long-term daily infusions of combination of anti-TB drugs compared with their usual daily injections is safe and effective method of intravenous therapy. It is not accompanied by subjective complaints of patients and the development of phlebitis, which leads to early sputum conversion. With daily injections of veins 56.2 % of patients prematurely discontinued treatment through intensive local complications or phlebitis. Application of intensive treatment with the introduction of anti-TB drugs allows for faster time to achieve sputum conversion.

Safety and efficiency of the port-catheter for intensive intravenous chemotherapy in patients with multi-drug resistant tuberculosis and extensively drug-resistant tuberculosis

PURPOSE. To study the efficacy and tolerability of the port catheter for continuous intravenous infusion in patients with MDR-TB and XDR-TB.&#x0D; MATERIALS AND METHODS. In a controlled study examined the effectiveness of the port catheter during an intensive 7-component anti-TB treatment with intravenous application of 3 anti-TB drugs (moxifloxacin, PAS, linezolid) in 16 patients with MDR-TB and XDR-TB. In the comparison group, which is formed by a pair of matching according to the drug resistance profile of MTB, the same intensive chemotherapy regimens in which the infusion of these drugs was carried out by daily injections of veins. In each group dominated patients with retreatment cases — 14 (87.5 %) patients. The planned duration of intravenous therapy was 2—4 months.&#x0D; RESULTS. Port-catheter for continuous infusion of combination of anti-tuberculosis drugs in comparison to their administration in the usual way ensures high efficiency and safety. In any case, was not observed phlebitis, no complaints of pain at the injection site, only 12.5 % cases were hematoma after setting the port in comparison to 100.0 % of patients with daily venous injections. In the study group was not a single case of interruption of intravenous infusion. In the control group, 56.2 % of patients discontinued intravenous treatment due to inability to penetrate the vein, patient’s complaints pain or phlebitis. At the end of the intensive phase of chemotherapy sputum conversion and disappearance of clinical symptoms were observed in 15 (3.7 %) patients of the study group, that was 26.7 % higher, than in control group (p&gt;0,05). We found significant difference in terms of sputum conversion, which occurred in the study group through (2,2±0,1) months vs (3,7±0,3) months (&lt;0,05) in control group.&#x0D; CONCLUSIONS. Port-catheter for long-term daily infusions of combination of anti-TB drugs compared with their usual daily injections is safe and effective method of intravenous therapy. It is not accompanied by subjective complaints of patients and the development of phlebitis, which leads to early sputum conversion. With daily injections of veins 56.2 % of patients prematurely discontinued treatment through intensive local complications or phlebitis. Application of intensive treatment with the introduction of anti-TB drugs allows for faster time to achieve sputum conversion.

Clinical Pharmacokinetics and Pharmacodynamics of Ceftazidime-Avibactam Combination: A Model-Informed Strategy for its Clinical Development.

Avibactam is a non-β-lactam, β-lactamase inhibitor of the diazabicyclooctane class that covalently acylates its β-lactamase targets, encompassing extended spectrum of activities that cover serine β-lactamases but not metallo-β-lactamases. Ceftazidime and avibactam have complementary pharmacokinetic (PK) profiles. Both drugs have a half-life of approximately 2 h, making them suitable to be combined in a fixed-dose combination ratio of 4:1 (ceftazidime:avibactam). Renal clearance is the primary elimination pathway of both ceftazidime and avibactam, and dose adjustment is required in patients with moderate and severe renal impairment. Population PK models of ceftazidime and avibactam were developed separately and incorporated body weight, disease state, ethnicity, and renal function (creatinine clearance) as covariates of clearance and volume of distribution. The clinical dosing regimen of ceftazidime/avibactam combination was determined from population PK model simulations in the patient population for dosing regimens that can achieve sufficient joint probability of target attainment for ceftazidime minimum inhibitory concentration (MIC) of 8mg/L at a fixed 4mg/L avibactam concentration (MIC ≤ 8/4mg/L); 8mg/L is the breakpoint of ceftazidime in Enterobacteriaceae and Pseudomonas aeruginosa for the target pharmacodynamic indices of ceftazidime and avibactam of 50% time at which the free ceftazidime concentration is above the MIC (fT > MIC) and 50% time at which the free avibactam is above a threshold concentration of 1mg/L (fT > CT). Whereas the static index approach does not take into account the changing potency of ceftazidime in the presence of changing avibactam concentration, a mathematical model based on kill-curve kinetics was utilized to validate the dose selection in humans. The clinical dosing regimen of 2/0.5g ceftazidime/avibactam administered every 8h as a 2-h intravenous infusion in patients with normal renal function, with dose adjustment in renal impairment, demonstrated statistical non-inferiority to carbapenem in phase III studies on the treatment of complicated intra-abdominal infection, complicated urinary tract infection, and nosocomial pneumonia, including ceftazidime non-susceptible Gram-negative pathogens. The success of the phase III studies validated the dose selection and exposure target that were associated with efficacy based on a model-informed approach.

Effect of Serial Infusions of CER-001, a Pre-β High-Density Lipoprotein Mimetic, on Coronary Atherosclerosis in Patients Following Acute Coronary Syndromes in the CER-001 Atherosclerosis Regression Acute Coronary Syndrome Trial

CER-001 is a negatively charged, engineered pre-β high-density lipoprotein (HDL) mimetic containing apolipoprotein A-I and sphingomyelin. Preliminary studies demonstrated favorable effects of CER-001 on cholesterol efflux and vascular inflammation. A post hoc reanalysis of a previously completed study of intravenous infusion of CER-001, 3 mg/k, showed that the intravenous infusion in patients with a high coronary plaque burden promoted regression as assessed by intravascular ultrasonography. To determine the effect of infusing CER-001 on coronary atherosclerosis progression in statin-treated patients. A double-blind, randomized, multicenter trial evaluating the effect of 10 weekly intravenous infusions of CER-001, 3 mg/kg, (n = 135) or placebo (n = 137) in patients with an acute coronary syndrome (ACS) and baseline percent atheroma volume (PAV) greater than 30% in the proximal segment of an epicardial artery by intravascular ultrasonography. The study included 34 academic and community hospitals in Australia, Hungary, the Netherlands, and the United States in patients with ACS presenting for coronary angiography. Patients were enrolled from August 15, 2015, to November 19, 2016. Participants were randomized to receive weekly CER-001, 3 mg/kg, or placebo for 10 weeks in addition to statins. The primary efficacy measure was the nominal change in PAV from baseline to day 78 measured by serial intravascular ultrasonography imaging. The secondary efficacy measures were nominal change in normalized total atheroma volume and percentage of patients demonstrating plaque regression. Safety and tolerability were also evaluated. Among 293 patients (mean [SD] age, 59.8 [9.4] years; 217 men [79.8%] and 261 white race/ethnicity [96.0%]), 86 (29%) had statin prior use prior to the index ACS and 272 (92.8%) had evaluable imaging at follow-up. The placebo and CER-001 groups had similar posttreatment median levels of low-density lipoprotein cholesterol (74 mg/dL vs 79 mg/dL; P = .15) and high-density lipoprotein cholesterol (43 mg/dL vs 44 mg/dL; P = .66). The primary efficacy measure, PAV, decreased 0.41% with placebo (P = .005 compared with baseline), but not with CER-001 (-0.09%; P = .67 compared with baseline; between group differences, 0.32%; P = .15). Similar percentages of patients in the placebo and CER-001 groups demonstrated regression of PAV (57.7% vs 53.3%; P = .49). Infusions were well tolerated, with no differences in clinical and laboratory adverse events observed between treatment groups. Infusion of CER-001 did not promote regression of coronary atherosclerosis in statin-treated patients with ACS and high plaque burden. ClinicalTrials.gov Identifier: NCT2484378.

An open-label, first-in-human, dose escalation study of a novel CD3-CD123 bispecific T-cell engager administered as a single agent by intravenous infusion in patients with relapsed or refractory acute myeloid leukemia, B-cell acute lymphoblastic leukemia, or high risk myelodysplastic syndrome.

TPS7076Background: Persistence of leukemic stem cells is an important cause of relapse in patients with acute myeloid leukemia (AML). CD123 (α-chain of the interleukin-3 receptor) is highly express...

Post Mastectomy Pain is No Longer Nightmare

Background PMPS nowadays is common due to advances in both; diagnosis and treatment of cancer breast. Choosing proper treatments can improve the patients’ quality of life. Cancer breast is common and quite important disease and female in our family must be aware of it. Improvement of the diagnosis and treatment PMPS lead to increased patient’s satisfaction and decrease fear of cancer breast. Objective Discuss different methods for management of PMPS with less side effects, adequate analgesia, improvement of quality of life, and better patient satisfaction in the future. Methods Treatment approaches include both pharmacological interventions and non-pharmacological strategies. However, current treatments of the PMPS are near-optimal and prevention much better than treatment. Conclusion Continuous perioperative thoracic epidural Fentanyl–bupivacaine infusion was much better in pain relief, less sedating effect and shorter duration of hospital and ICU stay than continuous perioperative entanyl intravenous infusion in patients undergoing major upper gastrointestinal cancer surgery.

Continuous Perioperative Thoracic Epidural Fentanyl-Bupivacaine Infusion vs. Continuous Perioperative Fentanyl Intravenous Infusion in Patients Undergoing Major Upper Abdominal Cancer Surgeries

Background: Major upper gastrointestinal cancer surgeries induce postoperative pain, that if not controlled may cause various organ dysfunctions and prolonged hospital and ICU stay. Thus an appropriate pain therapy to those patients must be applicated. Objective: To compares the effects of continuous perioperative thoracic epidural Fentanyl-bupivacaine infusion versus continuous perioperative Fentanyl intravenous infusion in patients undergoing major upper gastrointestinal cancer surgery. Methods: 60 patients (ASA II) of either sex were scheduled for elective upper gastrointestinal cancer surgeries. Patients were allocated randomly into two groups (30 patients each) to receive: continuous peri-operative epidural infusion with bupivacaine 0.132 and fentanyl (TEA group), or continuous peri-operative intravenous infusion with fentanyl (control group). Postoperative pain was assessed over 72 h using visual analogue scale (VAS). The intra and post-operative haemodynamic, sedation score and overall patient fentanyl consumption were recorded. Any concomitant events like nausea; vomiting, pruritus or respiratory complications were recorded postoperatively. Results: There was a significant decrease in pain sensation in TEA group during first day postoperative. Patient haemodynamics was significantly decreased in TEA group. As regard sedation scale, patients of the TEA group were significantly less sedated than control group at immediate postoperative only. Conclusion: Continuous perioperative thoracic epidural Fentanyl-bupivacaine infusion was much better in pain relief, less sedating effect and shorter duration of hospital and ICU stay than continuous perioperative fentanyl intravenous infusion in patients undergoing major upper gastrointestinal cancer surgery.

Analgesic efficacy, adverse effects, and safety of oxycodone administered as continuous intravenous infusion in patients after total hip arthroplasty.

BackgroundTotal hip arthroplasty (THA) causes extensive tissue damage and severe pain. This study aimed to assess the analgesic efficacy, adverse effects (AEs), and safety of continuous intravenous (iv) oxycodone infusion with ketoprofen (injected into the iv line) in patients after THA, and to assay serum oxycodone levels.Patients and methodsFourteen patients, aged 59‒82 years with American Society of Anesthesiologists (ASA) classification I or III, underwent THA with intrathecal analgesia and sedation induced by iv propofol. After the surgery, oxycodone (continuous iv infusion) at a dose of 1 mg/h (five patients) or 2 mg/h (nine patients) with 100 mg ketoprofen (injected into the iv line) was administered to each patient every 12 h. Pain was assessed using a numerical rating scale (NRS: 0 – no pain, 10 – the most severe pain) at rest and during movement. AEs, including hemodynamic unsteadiness, nausea, vomiting, pruritus, cognitive impairment, and respiratory depression, were registered during the first 24 h after surgery.ResultsOxycodone (continuous iv infusion) at a dose of 2 mg/h with ketoprofen (100 mg) administered every 12 h provided satisfactory analgesia in all nine patients without the need of rescue analgesics within the first 24 h after THA. In three out of five patients, oxycodone at 1 mg/h was effective. Oxycodone did not induce drowsiness, vomiting, pruritus, respiratory depression, or changes in blood pressure. Bradycardia appeared in two patients, and nausea was observed in one patient.ConclusionOxycodone infusion with ketoprofen administered by iv is effective in patients after THA. Intravenous infusion of oxycodone is a predictable, stable, and safe method of drug administration.

An observational time and motion study of denosumab subcutaneous injection and zoledronic acid intravenous infusion in patients with metastatic bone disease: results from three European countries

PurposeDenosumab (administered via subcutaneous injection) demonstrated superior efficacy versus the intravenously administered zoledronic acid in the prevention of skeletal-related events in an integrated analysis of three head-to-head phase III trials in patients with bone metastases secondary to solid tumors. To date, no studies have evaluated treatment administration duration endpoints of these two agents.MethodsA multinational, multi-site, observational time and motion study conducted in 10 day oncology units (DOUs) across Belgium, Germany, and Italy. Observations of process time included task time and active healthcare professional (HCP) time for pre-defined tasks. Patient time measurements included entering/exiting the DOU, treatment room, and treatment chair or examination table.ResultsA total of 189 patients were enrolled (82 received zoledronic acid and 107 received denosumab) and 238 observations were recorded (104 for zoledronic acid and 134 for denosumab). Mean total task time was reduced by 81% when denosumab was used versus zoledronic acid (8.4 versus 44.2 min; p < 0.0001; pooled analysis across all countries). Pooled estimates for active HCP time were 12.2 min for zoledronic acid and 6.9 min for denosumab (44% reduction; p < 0.0001).ConclusionsIn the countries studied, using denosumab compared with zoledronic acid reduced total task time and active HCP time. Thus, HCPs have more time to dedicate to other patients or care activities. An ability to increase the volume of appointments within DOUs could reduce waiting lists in sites operating at full capacity and increase overall productivity and efficiency in hospital processes.