ABSTRACT
Background: The COVID-STEROID 2 trial found high probability of benefit with dexamethasone 12 mg vs. 6 mg daily among patients with COVID-19 and severe hypoxemia. There was suggestion of heterogeneity of treatment effects (HTE)between patients enrolled from Europe vs. India on the primary outcome. Whether there was HTE by geographical region for the remaining prespecified patient-important outcomes is unclear. Methods: We evaluated HTE by geographical region (Europe vs. India) for all secondary outcomes assessed in the trial with analyses adjusted for stratification variables. The results are presented as risk differences (RDs) or mean differences (MDs) with 99% confidence intervals (CIs) and P-values from interaction tests. Results: We found HTE for mortality at day 28 (RD for Europe -8.3% (99 % CI: -17.7 to 1.0) vs. RD for India 0.1% (99% CI: -10.0 to 10.0)), mortality at day 90 (RD for Europe -7.4% (99% CI: -17.1 to 2.0) vs. RD for India -1.4% (99% CI:-12.8 to 9.8)), mortality at day 180 (RD for Europe -6.7% (99%CI:-16.4 to 2.9) vs. RD for India -1.0% (99%CI:-12.3 to 10.3)), and number of days alive without life support at day 90 (MD for Europe 6.1 days (99% CI:-1.3 to 13.4) vs. MD for India 1.7 days (99% CI:-8.4 to11.8)). For serious adverse reactions, the direction was reversed (RD for Europe -1.0% (99% CI:-7.1 to 5.2) vs. RD for India -5.3% (99% CI: -16.2 to 5.0). For HRQoL outcomes, MD in EQ-5D-5L index values was 0.08(99%CI: -0.01 to 0.16) for Europe and 0.02(99%CI:-0.10 to 0.14) for India. For EQ VAS, MD was 4.4(95%CI:-3.1 to 11.9) for Europe and 2.6(99%CI:-9.0 to 14.2) for India. P values for all tests of interaction were [≥]0.12. Conclusions: In this post hoc exploratory analysis, we found that higher dose dexamethasone may have lower beneficial effects for patients in India as compared with those in Europe without an increase in serious adverse reactions.
Subject(s)
COVID-19 , Hypoxia , Neural Tube DefectsABSTRACT
Background SARS-CoV-2 infection is associated with a significant risk of hospitalisation, death, and prolonged impact on quality of life. Evaluation of new treatment options and optimising therapeutic management of people hospitalised with SARS-CoV-2 infection remains essential, but rapid changes in pandemic conditions and potential therapies have limited the utility of traditional approaches to randomised controlled trials.Methods ASCOT ADAPT is an international, investigator-initiated, adaptive platform, randomised controlled trial of therapeutics for non-critically ill patients hospitalised with COVID-19. The study design is open label and pragmatic. Potential participants are hospitalised adults with PCR confirmed, symptomatic, SARS-CoV-2 infection, within 14 days of symptom onset. Domains include antiviral, antibody and anticoagulant interventions, with a composite primary outcome of 28-day mortality or progression to intensive-care level respiratory or haemodynamic support. Initial interventions include intravenous nafamostat and variable dose anticoagulation. A range of secondary endpoints, and substudies for specific domains and interventions are outlined.Discussion This paper presents the trial protocol and management structure, including international governance, remote site monitoring and biobanking activities, and provides commentary on ethical and pragmatic considerations in establishing the ASCOT ADAPT trial under pandemic conditions.
Subject(s)
COVID-19ABSTRACT
Background: Healthcare workers (HCWs),particularly from lower-middle income countries (LMIC), are at high risk of acquiring COVID-19. Limited data exist on the effectiveness of hydroxychloroquine as prophylaxis. Our trial evaluated the effectiveness of a 12-week regimen of hydroxychloroquine among HCWs on the risk of laboratory-confirmed COVID-19 in the 6 months after randomization Methods: We conducted a multicentre parallel-group open-label randomized controlled trial in 9 centres across India. HCWs serving in an environment with exposure to COVID-19 were eligible and randomized in a 1:1 ratio to hydroxychloroquine plus standard practice or to standard practice alone (role-appropriate personal protective equipment). In the intervention arm, participants received 2 doses of 400mg hydroxychloroquine at randomization followed by a weekly dose for 12 weeks. The primary outcome was the proportion of laboratory-confirmed COVID-19 in the 6 months after randomization using an intention-to-treat analysis. The trial was registered on Clinical Trials Registry of India(CTRI/2020/05/025067). Findings: From 29th June 2020 to 4th February 2021, 886 participants were screened and 416 were randomized (203-standard practice and 213- hydroxychloroquine plus standard practice). In the 6 months after randomization (primary analysis population=413), 11 participants assigned to the hydroxychloroquine group and 12 participants assigned to the standard practice group met the primary end point[ 5.1% vs 5.9%; OR 0.85, [95% CI 0.35-2.06] p=0.71]. There was no heterogeneity of treatment effect on the primary outcome in any of the pre-specified subgroups. There were no significant differences in any of the secondary outcomes. The adverse event rates were 9.9% and 6.9% in the hydroxychloroquine and standard practice arms respectively. There were no serious adverse events in either group. Interpretation: Hydroxychloroquine along with standard practice was not superior to standard practice alone on the proportion of lab-confirmed COVID-19. However, conclusions are limited by the premature trial cessation.Trial Registration: Clinical Trials Registry of India (CTRI/2020/05/025067).Funding: Wesley Medical Research, AustraliaDeclaration of Interest: OJ reports being a member of the WHO R&D Blueprint Safety Monitoring Team, ACT Acclerator-R&D Digital Health working group and COVID-19 Clinical Research Coalition data sharing working group. Remaining authors have nothing to declare. Ethical Approval: Written informed consent was obtained from all participants. Thetrial was approved by the Ethics Committee at all participating sites (coordinating centre EC approval number: The George Institute Ethics Committee:08-2020)
Subject(s)
COVID-19ABSTRACT
The advent of COVID-19 has kept the whole world on their toes. Countries are maximizing their efforts to combat the virus and to minimize the infection. Since infectious microorganisms may be transmitted by variety of routes, respiratory and facial protection is required for those that are usually transmitted via droplets/aerosols. Therefore this pandemic has caused a sudden increase in the demand for personal protective equipment (PPE) such as gloves, masks, and many other important items since, the evidence of individual-to-individual transmission (through respiratory droplets/coughing) and secondary infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). But the disposal of these personal protective measures remains a huge question mark towards the environmental impact. Huge waste generation demands proper segregation according to waste types, collection, and recycling to minimize the risk of infection spread through aerosols and attempts to implement measures to monitor infections. Hence, this review focuses on the impact of environment due to improper disposal of these personal protective measures and to investigate the safe disposal methods for these protective measures by using the safe, secure and innovative biological methods such as the use of Artificial Intelligence (AI) and Ultraviolet (UV) lights for killing such deadly viruses.