Double-Blind Randomized Clinical Trial to Examine the Pharmacokinetic and Clinical Impacts of Fixed Dose versus Weight-based Enoxaparin Prophylaxis: A Methodologic Description of the FIxed or Variable Enoxaparin (FIVE) Trial.
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SUBMITTER: Pannucci CJ
PROVIDER: S-EPMC6554177 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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Double-Blind Randomized Clinical Trial to Examine the Pharmacokinetic and Clinical Impacts of Fixed Dose versus Weight-based Enoxaparin Prophylaxis: A Methodologic Description of the FIxed or Variable Enoxaparin (FIVE) Trial.
Pannucci Christopher J CJ Fleming Kory I KI Bertolaccini Corinne C Prazak Ann Marie AM Stoddard Gregory J GJ Momeni Arash A
Plastic and reconstructive surgery. Global open 20190411 4
Venous thromboembolism is an important patient safety in plastic surgery, and multiple clinical trials in the past 10 years have provided increased understanding of the risks and benefits of venous thromboembolism prevention strategies. This paper provides an exhaustive discussion of the rationale behind and methodology for an in progress randomized double-blind clinical trial in plastic surgery inpatients, in which the 2 study arms are enoxaparin 40 mg twice daily and enoxaparin 0.5 mg/kg twice ...[more]
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Project description:ImportanceBetween 4% and 12% of patients undergoing colorectal surgery and receiving enoxaparin, 40 mg per day, have a postoperative venous thromboembolism (VTE) event. An improved understanding of why "breakthrough" VTE events occur despite guideline-compliant prophylaxis is an important patient safety question.ObjectiveTo determine the proportion of patients undergoing colorectal surgery who received adequate anticoagulation based on peak anti-factor Xa (aFXa) levels while receiving enoxaparin at 40 mg per day.Design, setting, and participantsThis prospective, nonrandomized clinical trial was conducted between February 2017 and July 2018 with 90-day follow-up at a quaternary academic medical center in the Intermountain West and included patients undergoing colorectal surgery who had surgery after receiving general anesthesia, were admitted for at least 3 days, and received enoxaparin, 40 mg once daily.InterventionsAll patients had aFXa levels measured after receiving enoxaparin 40 mg per day. Patients whose aFXa level was out of range entered the trial's interventional arm where real-time enoxaparin dose adjustment and repeated aFXa measurement were performed.Main outcomes and measuresPrimary outcome: in-range peak aFXa levels (goal range, 0.3-0.5 IU/mL) with enoxaparin, 40 mg per day. Secondary outcomes: (1) in-range trough aFXa levels (goal range, 0.1-0.2 IU/mL) and (2) the proportion of patients with in-range peak aFXa levels from enoxaparin, 40 mg once daily, vs the real-time enoxaparin dose adjustment protocol.ResultsOver 16 months, 116 patients undergoing colorectal surgery (65 women [56.0%]; 99 white individuals [85.3%], 13 Hispanic or Latino individuals [11.2%], and 4 Pacific Islander individuals [3.5%]; mean [range] age, 52.1 [18-85] years) were enrolled. Among 106 patients (91.4%) whose peak aFXa level was appropriately drawn, 72 (67.9%) received inadequate anticoagulation (aFXa < 0.3 IU/mL) with enoxaparin, 40 mg per day. Weight and peak aFXa levels were inversely correlated (r2 = 0.38). Forty-seven patients (77%) had a trough aFXa level that was not detectable (ie, most patients had no detectable level of anticoagulation for at least 12 hours per day). Real-time enoxaparin dose adjustment was effective. Patients were significantly more likely to achieve an in-range peak aFXa with real-time dose adjustment as opposed to fixed dosing alone (85.4% vs 29.2%, P < .001).Conclusions and relevanceThis study supports the finding that most patients undergoing colorectal surgery receive inadequate prophylaxis from enoxaparin, 40 mg once daily. These findings may explain the high rate of "breakthrough" VTE observed in many clinical trials.Trial registrationClinicalTrials.gov identifier: NCT02704052.
| S-EPMC6537829 | biostudies-literature
Project description:BackgroundThere is considerable debate regarding the ideal agent for venous thromboembolism (VTE) prophylaxis after TKA. Numerous studies and meta-analyses have yet to provide a clear answer and often omit one or more of the commonly used agents such as aspirin, warfarin, enoxaparin, and factor Xa inhibitors.Questions/purposesUsing a large database analysis, we asked: (1) What are the differences in VTE incidence in primary TKA after administration of aspirin, warfarin, enoxaparin, or factor Xa inhibitors? (2) What are the differences in bleeding risk among these four agents? (3) How has use of these agents changed with time?MethodsWe queried a combined Humana and Medicare database between 2007 and Quarter 1 of 2016, and identified all primary TKAs performed using ICD-9 and Current Procedural Terminology codes. All patients who had any form of antiplatelet or anticoagulation prescribed within 1 year before TKA were excluded from our study cohort. We then identified patients who had either aspirin, warfarin, enoxaparin, or factor Xa inhibitors prescribed within 2 weeks of primary TKA. Each cohort was matched by age and sex. Elixhauser comorbidities and Charlson Comorbidity Index for each group were calculated. We identified 1016 patients with aspirin, and age- and sex-matched 6096 patients with enoxaparin, 6096 patients with warfarin, and 5080 patients with factor Xa inhibitors. Using ICD-9 codes, with the understanding that patients at greater risk may have had more-attentive surveillance, the incidence of postoperative deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding-related complications (bleeding requiring surgical intervention, hemorrhage, hematoma, hemarthrosis), postoperative anemia, and transfusion were identified at 2 weeks, 30 days, 6 weeks, and 90 days postoperatively. A four-way chi-squared test was used to determine statistical significance. Utilization was calculated using compound annual growth rate.ResultsThere was a difference in the incidence of DVT at 90 days (p < 0.01). Factor Xa inhibitors (2.9%) had the lowest incidence of DVT followed by aspirin (3.0%) and enoxaparin (3.5%), and warfarin (4.8%). There was a difference in the incidence of PE at 90 days (p < 0.01). Factor Xa inhibitors (0.9%) had the lowest incidence of PE followed by enoxaparin (1.1%), aspirin (1.2%), and warfarin (1.6%). There was a difference in the incidence of postoperative anemia at 90 days (p < 0.01). Aspirin (19%) had the lowest incidence of postoperative anemia followed by warfarin (22%), enoxaparin (23%), and factor Xa inhibitors (23%). There was a difference in the incidence of a blood transfusion at 90 days (p < 0.01). Aspirin (7%) had the lowest incidence of a blood transfusion followed by factor Xa inhibitors (9%), warfarin (12%), and enoxaparin (13%). There were no differences in bleeding-related complications (p = 0.81) between the groups. Aspirin use increased at a compound annual growth rate of 30%, enoxaparin at 3%, and factor Xa inhibitors at 43%, while warfarin use decreased at a compound annual growth rate of -3%.ConclusionsFactor Xa inhibitors had the highest growth in utilization during our study period, followed by aspirin, when compared with enoxaparin and warfarin. When selected for the right patient, factor Xa inhibitors provided improved VTE prophylaxis compared with enoxaparin and warfarin, with a lower rate of blood transfusion. Aspirin provided comparable VTE prophylaxis compared with factor Xa inhibitors with improved VTE prophylaxis compared with enoxaparin and warfarin with the lowest risk of bleeding.Level of evidenceLevel III, therapeutic study.
| S-EPMC5539035 | biostudies-literature
Project description:BackgroundVenous thromboembolism (VTE) is a leading cause of maternal mortality and morbidity, with the highest incidence occurring during the postpartum period. This study compared the ability of two types of low-molecular-weight heparin, enoxaparin and bemiparin, to decrease the incidence of VTE following elective caesarean section, emergency caesarean section, and vaginal delivery in women who had risk factors for thromboembolism.MethodsIn this prospective clinical trial using a sequential group allocation method, 7020 haemodynamically stable women delivered vaginally or abdominally at the Maternity Teaching Hospital, Kurdistan region, Erbil, Iraq, between May 1, 2012, and November 1, 2013. These women had risk factors for VTE and were allocated to the following groups: treatment with 3500 IU/day of bemiparin, 4000 IU/day of enoxaparin, or no intervention (control). The first dose was administered 6 hours after vaginal or abdominal delivery, or 8 hours after delivery in women receiving spinal anaesthesia. Subsequent doses were administered daily for up to 6 days. The incidence of VTE was assessed for up to 40 days postpartum. Data were analyzed using the Statistical Package for Social Sciences version 19. Proportions were compared using the chi square test of association or Fisher's exact test. Binary logistic regression analysis was used with VTE as the dependent variable.ResultsVTE occurred in 1 (0.042%) woman in the bemiparin group, two (0.085%) women in the enoxaparin group, and nine (0.384%) women in the control group (P = 0.017). Regression analysis showed that women on bemiparin (OR = 0.106; 95% CI = 0.013-0.838) and enoxaparin (OR = 0.226; 95% CI = 0.049-1.049) were at lower risk of developing VTE than control women. Adverse events in the enoxaparin group included wound dehiscence, haematoma, and separation. None of these occurred in the bemiparin group.ConclusionsPostpartum bemiparin is significantly effective as a prophylaxis for VTE. Wound complications develop after use of enoxaparin, but not after bemiparin.Trial registrationClinicalTrials.gov; Identifier: NCT01588171 ; date: April 26, 2012.
| S-EPMC4377203 | biostudies-literature
Project description:BACKGROUND:Phenylephrine is the most commonly used vasopressor for prophylaxis against maternal hypotension during cesarean delivery; however, the best regimen for its administration is not well established. Although variable infusion protocols had been suggested for phenylephrine infusion, evidence-based evaluation of variable infusion regimens are lacking. The aim of this work is to compare variable infusion, fixed on-and-off infusion, and intermittent boluses of phenylephrine for prophylaxis against maternal hypotension during cesarean delivery. METHODS:A randomized controlled study was conducted, including full-term pregnant women scheduled for elective cesarean delivery. Participants were divided into three groups which received phenylephrine by either intermittent boluses (1.5 mcg/Kg phenylephrine), fixed on-and-off infusion (with a dose of 0.75 mcg/Kg/min), or variable infusion (with a starting dose of 0.75 mcg/Kg/min). The three groups were compared with regard to frequency of: maternal hypotension (primary outcome), second episode hypotension, reactive hypertension, and bradycardia. Other outcomes included heart rate, systolic blood pressure, physician interventions, and neonatal outcomes. RESULTS:Two-hundred and seventeen mothers were available for final analysis. The 2 infusion groups showed less incidence of maternal hypotension {26/70 (37%), 22/71 (31%), and (51/76 (67%)} and higher incidence of reactive hypertension compared to the intermittent boluses group without significant differences between the two former groups. The number of physician interventions was highest in the variable infusion group compared to the other two groups. The intermittent boluses group showed lower systolic blood pressure and higher heart rate compared to the two infusion groups; whilst the two later groups were comparable. CONCLUSION:Both phenylephrine infusion regimens equally prevented maternal hypotension during cesarean delivery compared to intermittent boluses regimen. Due to higher number of physician interventions in the variable infusion regimen, the current recommendations which favor this regimen over fixed infusion regimen might need re-evaluation.
| S-EPMC6827237 | biostudies-literature
Project description:Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial
| PRJEB20349 | ENA
Project description:BackgroundWe aimed to examine the efficiency of fixed daily dose enoxaparin (40 mg) thromboprophylaxis strategy for patients undergoing inpatient rehabilitation.MethodsThis was an observational, prospective, cohort study that included 63 hospitalized patients undergoing rehabilitative treatment following sub-acute ischemic stroke (SAIS) or spinal cord injury (SCI), with an indication for thromboprophylaxis. Anti-Xa level measured three hours post-drug administration (following three consecutive days of enoxaparin treatment or more) was utilised to assess in vivo enoxaparin activity. An anti-Xa level between 0.2-0.5 U/ml was considered evidence of effective antithrombotic activity.ResultsWe found sub-prophylactic levels of anti-Xa (<0.2 U/ml) in 19% (12/63). Results were within the recommended prophylactic range (0.2-0.5 U/ml) in 73% (46/63) and were supra-prophylactic (>0.5 U/ml) in 7.9% (5/63) of patients. Anti-Xa levels were found to inversely correlate with patients' weight and renal function as defined by creatinine clearance (CrCl) (p<0.05).ConclusionsOur study confirmed that a one-size-fits-all approach for venous thromboembolism (VTE) prophylaxis may be inadequate for rehabilitation patient populations. The efficacy of fixed-dose enoxaparin prophylaxis is limited and may be influenced by renal function and weight. This study suggests that anti-Xa studies and prophylactic enoxaparin dose adjustments should be considered in certain patients, such as those who are underweight, overweight and or have suboptimal renal function.Trial registrationNo. NCT103593291, registered August 2018.
| S-EPMC10782744 | biostudies-literature
Project description:NK911 is a novel supramolecular nanocarrier designed for the enhanced delivery of doxorubicin (DXR) and is one of the successful polymer micelle systems to exhibit an efficient accumulation in solid tumours in mice. The purpose of this study was to define the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of NK911 and to evaluate its pharmacokinetic profile in man. NK911 was given intravenously to patients with solid tumours every 3 weeks using an infusion pump at a rate of 10 mg DXR equivalent min(-1). The starting dose was 6 mg DXR equivalent m(-2), and the dose was escalated according to the accelerated titration method. A total of 23 patients participated in this study. Neutropenia was the predominant haematological toxicity, and grade 3 or 4 neutropenia was observed at doses of 50 and 67 mg m(-2). Common nonhaematological toxicities were mild alopecia, stomatitis, and anorexia. In the dose identification part of the study, DLTs were observed at a dose of 67 mg m(-2) (grade 4 neutropenia lasting more than 5 days). Thus, this dosage level was determined to be the MTD. Infusion-related reactions were not observed in any cases. The C(5 min) and area under the concentration curve parameters of NK911 exhibited dose-dependent characteristics. Among the 23 patients, a partial response was obtained in one patient with metastatic pancreatic cancer. NK911 was well tolerated and produced only moderate nausea and vomiting at myelosuppressive dosages. The recommended phase II dose was determined to be 50 mg m(-2) every 3 weeks.
| S-EPMC2410050 | biostudies-other
Project description:EORTC 10994 is a phase III clinical trial comparing FEC with ET in patients with large operable, locally advanced or inflammatory breast cancer (www.eortc.be). Frozen biopsies were taken at randomisation. RNA was extracted from 100um thickness of 14G core needle biopsies. Adjacent sections were tested by H&E to confirm >20% tumour cell content. 100 ng total RNA per chip were amplified using the Affymetrix small sample protocol (IVT then Enzo). 49 tumours were tested on Affymetrix U133A chips. The CEL files were quantile normalised together using rma. Clinical response data are not available yet. Keywords = Apocrine carcinoma Keywords = breast cancer
2005-06-01 | GSE1561 | GEO
Project description:ImportanceThe Centers for Medicare & Medicaid Services requires health care organizations to report the National Clinical Trial (NCT) identifier on claims for items and services related to clinical trials that qualify for coverage. This same NCT identifier is used to identify clinical trials in the ClinicalTrials.gov registry. If linked, this information could facilitate population-based analyses of clinical trial participation and outcomes.ObjectiveTo evaluate the validity of a linkage between fee-for-service (FFS) Medicare claims and ClinicalTrials.gov through the NCT identifier for patients with cancer enrolled in clinical trials.Design, setting, and participantsThis cohort study included 2 complementary retrospective analyses for a validation assessment. First, billing data from 3 health care institutions were used to estimate the missingness of the NCT identifier in claims by calculating the proportion of known participants in cancer clinical trials with no NCT identifier on any submitted Medicare claims. Second, the Surveillance Epidemiology and End Results-Medicare data set, which includes a subset of all FFS Medicare beneficiaries for whom health insurance claims are linked with cancer registry data, was used to identify adult patients diagnosed with cancer between 2006 and 2015 with an NCT identifier in claims corresponding to an interventional cancer clinical trial. To estimate the accuracy of the NCT identifier when present, the proportion of NCT identifiers that corresponded to trials that were aligned with the patients' known primary or secondary diagnoses was calculated. Data were analyzed from March 2020 to March 2021.ExposuresAn NCT identifier present in Medicare claims.Main outcomes and measuresThe main outcome was participating in a clinical trial relevant to patient's cancer diagnosis.ResultsA total of 1 171 816 patients were included in analyses. Across the 3 participating institutions, there were 5061 Medicare patients enrolled in a clinical trial, including 3797 patients (75.0%) with an NCT identifier on at least 1 billing claim that matched the clinical trial on which the patient was participating. Among 1 171 816 SEER-Medicare patients, 29 138 patients (2.5%) had at least 1 claim with a value entered in the NCT identifier field corresponding to 32 950 unique patient-NCT identifier pairs. There were 26 694 pairs (81.0%) with an NCT identifier corresponding to a clinical trial registered in ClinicalTrials.gov, of which 10 170 pairs (38.1%) were interventional cancer clinical trials. Among these, 9805 pairs (96.4%) were considered appropriate.Conclusions and relevanceIn this cohort study, this data linkage provided a novel data source to study clinical trial enrollment patterns among Medicare patients with cancer on a population level. The presence of the NCT identifiers in claims for Medicare patients participating in clinical trials is likely to improve over time with increasing adherence with the Centers for Medicare & Medicaid Services mandate.
| S-EPMC8941352 | biostudies-literature
Project description:Venous thromboembolism (VTE) can be encountered by 60% of hospitalized patients. Anticoagulants have been recommended to reduce the risk of VTE in patients with risk factors. However, no specific dosing recommendations for obese patients are provided in the current practice guidelines. The purpose of this study was to determine the efficacy and safety of weight-based dosing of enoxaparin for VTE prophylaxis among morbidly obese patients undergoing surgery.Adult patients were enrolled if they have a body mass index (BMI) of ≥35 kg/m2 and were scheduled for surgery. These patients were prescribed enoxaparin (0.5 mg/kg subcutaneously [SC] once daily). Peak anti-factor Xa levels were measured 4 h after the third dose of enoxaparin. The primary outcome measure was to determine whether a weight-based dosing of enoxaparin of 0.5 mg/kg produce the anticipated peak anti-Xa levels (0.2-0.6 IU/m) among obese patients undergoing surgery. Secondary outcomes include the incidence of VTE, the incidence of minor or major bleeding, and the incidence of heparin-induced thrombocytopenia (HIT).Fifty patients were enrolled in the study. The mean age was 53 ± 16 years, 74% of the patients were female. The mean BMI was 40.5 ± 5, and the average enoxaparin dose was 50 ± 9.8 SC daily. Nearly 88% of the patients reached the target anti-factor Xa (0.427 ± 0.17). None of the patients developed HIT or VTE. There was no incidence of major or minor bleeding.Weight-based enoxaparin dose led to the anticipated peak anti-Xa levels (0.2-0.6 IU/mL) in most of the morbidly obese study patients undergoing surgery without any evidence of major side effects. The weight-based dosing of enoxaparin was also effective in preventing VTE in all patients. Although these results are promising, further comparative trials are needed in the setting of morbidly obese surgical patients.
| S-EPMC5541968 | biostudies-other