scholarly journals Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial)

BMJ ◽  
2020 ◽  
pp. m3939 ◽  
Author(s):  
Anup Agarwal ◽  
Aparna Mukherjee ◽  
Gunjan Kumar ◽  
Pranab Chatterjee ◽  
Tarun Bhatnagar ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Confidence Interval ◽  
Phase Ii ◽  
Controlled Trial ◽  
Severe Disease ◽  
A Priori ◽  
Standard Of Care ◽  
Open Label ◽  
All Cause Mortality ◽  
Randomised Controlled

Abstract Objective To investigate the effectiveness of using convalescent plasma to treat moderate coronavirus disease 2019 (covid-19) in adults in India. Design Open label, parallel arm, phase II, multicentre, randomised controlled trial. Setting 39 public and private hospitals across India. Participants 464 adults (≥18 years) admitted to hospital (screened 22 April to 14 July 2020) with confirmed moderate covid-19 (partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO 2 /FiO 2 ) ratio between 200 mm Hg and 300 mm Hg or a respiratory rate of more than 24/min with oxygen saturation 93% or less on room air): 235 were assigned to convalescent plasma with best standard of care (intervention arm) and 229 to best standard of care only (control arm). Interventions Participants in the intervention arm received two doses of 200 mL convalescent plasma, transfused 24 hours apart. The presence and levels of neutralising antibodies were not measured a priori; stored samples were assayed at the end of the study. Main outcome measure Composite of progression to severe disease (PaO 2 /FiO 2 <100 mm Hg) or all cause mortality at 28 days post-enrolment. Results Progression to severe disease or all cause mortality at 28 days after enrolment occurred in 44 (19%) participants in the intervention arm and 41 (18%) in the control arm (risk difference 0.008 (95% confidence interval −0.062 to 0.078); risk ratio 1.04, 95% confidence interval 0.71 to 1.54). Conclusion Convalescent plasma was not associated with a reduction in progression to severe covid-19 or all cause mortality. This trial has high generalisability and approximates convalescent plasma use in real life settings with limited laboratory capacity. A priori measurement of neutralising antibody titres in donors and participants might further clarify the role of convalescent plasma in the management of covid-19. Trial registration Clinical Trial Registry of India CTRI/2020/04/024775.

scholarly journals High dose oral and intravenous rifampicin for improved survival from adult tuberculous meningitis: a phase II open-label randomised controlled trial (the RifT study)

2018 ◽  
Vol 3 ◽  
pp. 83 ◽  
Author(s):  
Fiona V. Cresswell ◽  
Kenneth Ssebambulidde ◽  
Daniel Grint ◽  
Lindsey te Brake ◽  
Abdul Musabire ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Phase Ii ◽  
Controlled Trial ◽  
Standard Of Care ◽  
Hiv Positive ◽  
Current Standard ◽  
Open Label ◽  
Dose Oral ◽  
Randomised Controlled ◽  
Positive Population

Background: Tuberculous meningitis (TBM) has 44% (95%CI 35-52%) in-hospital mortality with standard therapy in Uganda. Rifampicin, the cornerstone of TB therapy, has 70% oral bioavailability and ~10-20% cerebrospinal fluid (CSF) penetration.  With current WHO-recommended TB treatment containing 8-12mg/kg rifampicin, CSF rifampicin exposures frequently fall below the minimal inhibitory concentration for M. tuberculosis. Two Indonesian phase II studies, the first investigating intravenous rifampicin 600mg and the second oral rifampicin ~30mg/kg, found the interventions were safe and resulted in significantly increased CSF rifampicin exposures and a reduction in 6-month mortality in the investigational arms. Whether such improvements can be replicated in an HIV-positive population remains to be determined. Protocol: We will perform a phase II, open-label randomised controlled trial, comparing higher-dose oral and intravenous rifampicin with current standard of care in a predominantly HIV-positive population. Participants will be allocated to one of three parallel arms (I:I:I): (i) intravenous rifampicin 20mg/kg for 2-weeks followed by oral rifampicin 35mg/kg for 6-weeks; (ii) oral rifampicin 35mg/kg for 8-weeks; (iii) standard of care, oral rifampicin 10mg/kg/day for 8-weeks. Primary endpoints will be: (i) pharmacokinetic parameters in plasma and CSF; (ii) safety. We will also examine the effect of higher-dose rifampicin on survival time, neurological outcomes and incidence of immune reconstitution inflammatory syndrome. We will enrol 60 adults with suspected TBM, from two hospitals in Uganda, with follow-up to 6 months post-enrolment. Discussion: HIV co-infection affects the bioavailability of rifampicin in the initial days of therapy, risk of drug toxicity and drug interactions, and ultimately mortality from TBM. Our study aims to demonstrate, in a predominantly HIV-positive population, the safety and pharmacokinetic superiority of one or both investigational arms compared to current standard of care. The most favourable dose may ultimately be taken forward into an adequately powered phase III trial. Trial registration: ISRCTN42218549 (24th April 2018)

scholarly journals Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial

BMJ ◽  
2020 ◽  
pp. m1849 ◽  
Author(s):  
Wei Tang ◽  
Zhujun Cao ◽  
Mingfeng Han ◽  
Zhengyan Wang ◽  
Junwen Chen ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Adverse Events ◽  
Controlled Trial ◽  
Severe Disease ◽  
Standard Of Care ◽  
Open Label ◽  
Intention To Treat ◽  
Safety Population ◽  
Randomised Controlled ◽  
Negative Conversion

AbstractObjectiveTo assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19).DesignMulticentre, open label, randomised controlled trial.Setting16 government designated covid-19 treatment centres in China, 11 to 29 February 2020.Participants150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone).InterventionsHydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively).Main outcome measureNegative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone.ResultsOf 150 patients, 148 had mild to moderate disease and two had severe disease. The mean duration from symptom onset to randomisation was 16.6 (SD 10.5; range 3-41) days. A total of 109 (73%) patients (56 standard of care; 53 standard of care plus hydroxychloroquine) had negative conversion well before 28 days, and the remaining 41 (27%) patients (19 standard of care; 22 standard of care plus hydroxychloroquine) were censored as they did not reach negative conversion of virus. The probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), similar to that in the standard of care group (81.3%, 71.2% to 89.6%). The difference between groups was 4.1% (95% confidence interval –10.3% to 18.5%). In the safety population, adverse events were recorded in 7/80 (9%) hydroxychloroquine non-recipients and in 21/70 (30%) hydroxychloroquine recipients. The most common adverse event in the hydroxychloroquine recipients was diarrhoea, reported in 7/70 (10%) patients. Two hydroxychloroquine recipients reported serious adverse events.ConclusionsAdministration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients.Trial registrationChiCTR2000029868.

scholarly journals INtravenous Contrast computed tomography versus native computed tomography in patients with acute Abdomen and impaired Renal functiOn (INCARO): a multicentre, open-label, randomised controlled trial - study protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e037928
Author(s):  
Panu Räty ◽  
Panu Mentula ◽  
Hanna Lampela ◽  
Taina Nykänen ◽  
Ilkka Helanterä ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Renal Function ◽  
Randomised Controlled Trial ◽  
Acute Abdomen ◽  
Impaired Renal Function ◽  
Controlled Trial ◽  
Open Label ◽  
Intravenous Contrast ◽  
All Cause Mortality ◽  
Randomised Controlled

IntroductionCT is the primary imaging option for acute abdominal pain in adults. Intravenous (IV) contrast media use improves CT quality but may cause post-contrast acute kidney injury (PC-AKI). Retrospective studies show no association between reduced baseline renal function and IV contrast CT, but, to our knowledge, no data from randomised controlled trials exist.Methods and analysisThe INCARO (INtravenous Contrast computed tomography versus native computed tomography in patients with acute Abdomen and impaired Renal functiOn) trial is a multicentre, open-label, parallel group, superiority, individually randomised controlled trial comparing IV contrast-enhanced CT to native CT in patients requiring emergency abdominal or body CT with impaired renal function defined as an estimated glomerular filtration rate (eGFR) of 15 to 45 mL/min/1.73 m2. The primary outcome is a composite of all-cause mortality or renal replacement therapy (RRT) within 90 days from CT. Secondary outcomes are AKI measured by KDIGO (The Kidney Disease: Improving Global Outcomes) criteria within 72 hours from CT, organ dysfunction defined by mSOFA (modified Sequential Organ Failure Assessment) criteria after 48 hours from CT, alive and hospital-free days within 90 days after CT, and time from imaging to definitive treatment. All-cause mortality, need for RRT and renal transplant in long-term follow-up are also measured. The calculated sample size is 994 patients. Patient recruitment is estimated to take 3 years.Ethics and disseminationThe Ethics Committee of Helsinki University Hospital approved the study. The findings will be disseminated in peer-reviewed academic journals.Trial registration numberNCT04196244

Sign in / Sign up

Export Citation Format

Share Document