scholarly journals Anti-Thrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC): Study design and methodology for an international, adaptive Bayesian randomized controlled trial

2020 ◽  
Vol 17 (5) ◽  
pp. 491-500 ◽  
Author(s):  
Brett L Houston ◽  
Patrick R Lawler ◽  
Ewan C Goligher ◽  
Michael E Farkouh ◽  
Charlotte Bradbury ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Invasive Mechanical Ventilation ◽  
Data Safety Monitoring Board ◽  
Primary Objective ◽  
Open Label ◽  
Randomized Controlled ◽  
Therapeutic Anticoagulation ◽  
Adaptive Trial

Background: Mortality from COVID-19 is high among hospitalized patients and effective therapeutics are lacking. Hypercoagulability, thrombosis and hyperinflammation occur in COVID-19 and may contribute to severe complications. Therapeutic anticoagulation may improve clinical outcomes through anti-thrombotic, anti-inflammatory and anti-viral mechanisms. Our primary objective is to evaluate whether therapeutic-dose anticoagulation with low-molecular-weight heparin or unfractionated heparin prevents mechanical ventilation and/or death in patients hospitalized with COVID-19 compared to usual care. Methods: An international, open-label, adaptive randomized controlled trial. Using a Bayesian framework, the trial will declare results as soon as pre-specified posterior probabilities for superiority, futility, or harm are reached. The trial uses response-adaptive randomization to maximize the probability that patients will receive the more beneficial treatment approach, as treatment effect information accumulates within the trial. By leveraging a common data safety monitoring board and pooling data with a second similar international Bayesian adaptive trial (REMAP-COVID anticoagulation domain), treatment efficacy and safety will be evaluated as efficiently as possible. The primary outcome is an ordinal endpoint with three possible outcomes based on the worst status of each patient through day 30: no requirement for invasive mechanical ventilation, invasive mechanical ventilation or death. Conclusion: Using an adaptive trial design, the Anti-Thrombotic Therapy To Ameliorate Complications of COVID-19 trial will establish whether therapeutic anticoagulation can reduce mortality and/or avoid the need for mechanical ventilation in patients hospitalized with COVID-19. Leveraging existing networks to recruit sites will increase enrollment and mitigate enrollment risk in sites with declining COVID-19 cases.

Probiotic prophylaxis to prevent ventilator associated pneumonia (VAP) in children on mechanical ventilation: an open-label randomized controlled trial

2015 ◽  
Vol 41 (4) ◽  
pp. 677-685 ◽  
Author(s):  
Balasubramaniam Banupriya ◽  
Niranjan Biswal ◽  
Rangan Srinivasaraghavan ◽  
Parameswaran Narayanan ◽  
Jharna Mandal
Keyword(s):  
Mechanical Ventilation ◽  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Ventilator Associated Pneumonia ◽  
Open Label ◽  
Randomized Controlled

scholarly journals Randomized Controlled Trial of the Safety and Efficacy of Daptomycin versus Standard-of-Care Therapy for Management of Patients with Osteomyelitis Associated with Prosthetic Devices Undergoing Two-Stage Revision Arthroplasty

2012 ◽  
Vol 56 (11) ◽  
pp. 5626-5632 ◽  
Author(s):  
Ivor Byren ◽  
Shruta Rege ◽  
Ed Campanaro ◽  
Sara Yankelev ◽  
Diane Anastasiou ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Clinical Success ◽  
Controlled Trial ◽  
Joint Infection ◽  
Revision Arthroplasty ◽  
Standard Of Care ◽  
Primary Objective ◽  
Open Label ◽  
Safety And Efficacy ◽  
Randomized Controlled

ABSTRACTThe prevalence ofStaphylococcus aureuscausing prosthetic joint infection (PJI) supports investigation of higher doses of daptomycin in the management of PJI. This was a prospective, randomized controlled trial studying safety and efficacy of daptomycin (6 and 8 mg/kg of body weight) compared with standard-of-care therapy for PJI. This open-label study randomized 75 patients undergoing 2-stage revision arthroplasty to daptomycin at 6 or 8 mg/kg or a comparator (vancomycin, teicoplanin, or semisynthetic penicillin). After prosthesis removal, patients received 6 weeks of antibiotic treatment and a 2- to 6-week antibiotic-free period before implantation of a new prosthesis. Test of cure (TOC) was within 1 to 2 weeks after reimplantation. The primary objective was evaluation of creatine phosphokinase (CPK) levels. Secondary objectives were clinical efficacy and microbiological assessments. Of 73 CPK safety population patients, CPK elevation of >500 U/liter occurred in 4 of 25 (16.0%) (daptomycin, 6 mg/kg) and 5 of 23 (21.7%) (daptomycin, 8 mg/kg) daptomycin-treated patients and 2 of 25 (8.0%) comparator patients. Adverse-event rates were similar among daptomycin and comparator groups. Among modified intent-to-treat patients at TOC, clinical success rates were 14 of 24 (58.3%) for 6 mg/kg daptomycin, 14 of 23 (60.9%) for 8 mg/kg daptomycin, and 8 of 21 (38.1%) for the comparator. Overall microbiological success at TOC was 12 of 24 (50.0%) for 6 mg/kg daptomycin, 12 of 23 (52.2%) for 8 mg/kg daptomycin, and 8 of 21 (38.1%) for comparator patients. In conclusion, daptomycin at 6 and 8 mg/kg given for up to 6 weeks was safe and appeared to be effective in managing staphylococcal PJI using a 2-stage revision arthroplasty technique in a total of 49 patients.

scholarly journals Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial.

2020 ◽  
Author(s):  
Peter Horby ◽  
Marion Mafham ◽  
Louise Linsell ◽  
Jennifer L Bell ◽  
Natalie Staplin ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Usual Care ◽  
Rate Ratio ◽  
Controlled Trial ◽  
Invasive Mechanical Ventilation ◽  
Open Label ◽  
Preliminary Results ◽  
Randomized Controlled ◽  
Increased Risk

Background: Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (COVID-19) on the basis of in vitro activity, uncontrolled data, and small randomized studies. Methods: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of hydroxychloroquine vs. usual care alone. The primary outcome was 28-day mortality. Results: 1561 patients randomly allocated to receive hydroxychloroquine were compared with 3155 patients concurrently allocated to usual care. Overall, 418 (26.8%) patients allocated hydroxychloroquine and 788 (25.0%) patients allocated usual care died within 28 days (rate ratio 1.09; 95% confidence interval [CI] 0.96 to 1.23; P=0.18). Consistent results were seen in all pre-specified subgroups of patients. Patients allocated to hydroxychloroquine were less likely to be discharged from hospital alive within 28 days (60.3% vs. 62.8%; rate ratio 0.92; 95% CI 0.85-0.99) and those not on invasive mechanical ventilation at baseline were more likely to reach the composite endpoint of invasive mechanical ventilation or death (29.8% vs. 26.5%; risk ratio 1.12; 95% CI 1.01-1.25). There was no excess of new major cardiac arrhythmia. Conclusions: In patients hospitalized with COVID-19, hydroxychloroquine was not associated with reductions in 28-day mortality but was associated with an increased length of hospital stay and increased risk of progressing to invasive mechanical ventilation or death.

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