scholarly journals An open label, randomised controlled trial of rifapentine versus rifampicin based short course regimens for the treatment of latent tuberculosis in England: the HALT LTBI pilot study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
J. Surey ◽  
H. R. Stagg ◽  
T. A. Yates ◽  
M. Lipman ◽  
P. J. White ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Pilot Trial ◽  
Latent Tuberculosis ◽  
Standard Of Care ◽  
Treatment Completion ◽  
Current Treatment ◽  
Open Label ◽  
Latent Tb Infection ◽  
Randomised Controlled ◽  
Urine Testing

Abstract Background Ending the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks. Methods An open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid (‘intervention’) or a daily combination of rifampicin/isoniazid (‘standard’), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded. Results Fifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7–91.4), compared with 19 of 25 (76.0%, CI 54.9–90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms. Conclusion In this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current treatment. Trial registration The trial was funded by the NIHR, UK and registered with ISRCTN (26/02/2013-No.04379941).

scholarly journals An Open Label, Randomised Controlled Trial of Rifapentine Versus Rifampicin Based Short Course Regimens for the Treatment of Latent Tuberculosis in England: The HALT LTBI Pilot Study

2020 ◽  
Author(s):  
Julian Surey ◽  
Helen R Stagg ◽  
Thomas A Yates ◽  
Marc Lipman ◽  
Peter J White ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Pilot Trial ◽  
Latent Tuberculosis ◽  
Standard Of Care ◽  
Treatment Completion ◽  
Open Label ◽  
Latent Tb Infection ◽  
Randomised Controlled ◽  
The Uk ◽  
Urine Testing

Abstract BackgroundEnding the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for twelve weeks. MethodsAn open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid (‘intervention’) or a daily combination of rifampicin/isoniazid (‘standard’), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded. Results52 patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8%, 95% confidence interval [CI] 57.7-91.4), compared with 19 of 25 (76.0%, CI 54.9-90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms. ConclusionIn this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current treatment.Trial RegistrationThe trial was funded by the NIHR, UK and registered with ISRCTN (26/02/2013-No.04379941).

scholarly journals Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manaf AlQahtani ◽  
Abdulkarim Abdulrahman ◽  
Abdulrahman Almadani ◽  
Salman Yousif Alali ◽  
Alaa Mahmood Al Zamrooni ◽  
...  
Keyword(s):  
Standard Therapy ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Severe Disease ◽  
Pilot Trial ◽  
Standard Of Care ◽  
Primary Outcome Measure ◽  
Secondary Outcome ◽  
Open Label ◽  
Plasma Therapy

AbstractConvalescent plasma (CP) therapy in COVID-19 disease may improve clinical outcome in severe disease. This pilot study was undertaken to inform feasibility and safety of further definitive studies. This was a prospective, interventional and randomized open label pilot trial in patients with severe COVID-19. Twenty COVID-19 patients received two 200 ml transfusions of convalescent patient CP over 24-h compared with 20 who received standard of care. The primary outcome was the requirement for ventilation (non-invasive or mechanical ventilation). The secondary outcomes were biochemical parameters and mortality at 28 days. The CP group were a higher risk group with higher ferritin levels (p < 0.05) though respiratory indices did not differ. The primary outcome measure was required in 6 controls and 4 patients on CP (risk ratio 0.67, 95% CI 0.22–2.0, p = 0.72); mean time on ventilation (NIV or MV) did not differ. There were no differences in secondary measures at the end of the study. Two patients died in the control and one patient in the CP arm. There were no significant differences in the primary or secondary outcome measures between CP and standard therapy, although a larger definitive study is needed for confirmation. However, the study did show that CP therapy appears to be safe in hospitalized COVID-19 patients with hypoxia.Clinical trials registration NCT04356534: 22/04/2020.

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 A multi centre randomized open label trial of chloroquine for the treatment of adults with SARS-CoV-2 infection in Vietnam

2020 ◽  
Vol 5 ◽  
pp. 141
Author(s):  
Evelyne Kestelyn ◽  
Nguyen Thi Phuong Dung ◽  
Yen Lam Minh ◽  
Le Manh Hung ◽  
Nguyen Minh Quan ◽  
...  
Keyword(s):  
Low Cost ◽  
Controlled Trial ◽  
Standard Of Care ◽  
Rapid Decline ◽  
Tolerability Profile ◽  
Open Label ◽  
Field Hospital ◽  
Novel Coronavirus ◽  
Randomised Controlled ◽  
Evidence Based Guidelines

Background: COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent COVID-19 or therapeutic agent to treat COVID-19. This clinical trial is designed to evaluate chloroquine as a potential therapeutic for the treatment of hospitalised people with COVID-19. We hypothesise that chloroquine slows viral replication in patients with COVID-19, attenuating the infection, and resulting in more rapid decline of viral load in throat/nose swabs. This viral attenuation should be associated with improved patient outcomes. Method: The study will start with a 10-patient prospective observational pilot study following the same entry and exclusion criteria as for the randomized trial and undergoing the same procedures. The main study is an open label, randomised, controlled trial with two parallel arms of standard of care (control arm) versus standard of care with 10 days of chloroquine (intervention arm) with a loading dose over the first 24 hours, followed by 300mg base orally once daily for nine days. The study will recruit patients in three sites in Ho Chi Minh City, Vietnam: the Hospital for Tropical Diseases, the Cu Chi Field Hospital, and the Can Gio COVID hospital. The primary endpoint is the time to viral clearance from throat/nose swab, defined as the time following randomization until the midpoint between the last positive and the first of the negative throat/nose swabs. Viral presence will be determined using RT-PCR to detect SARS-CoV-2 RNA. Discussion: The results of the study will add to the evidence-based guidelines for management of COVID-19. Given the enormous experience of its use in malaria chemoprophylaxis, excellent safety and tolerability profile, and its very low cost, if proved effective then chloroquine would be a readily deployable and affordable treatment for patients with COVID-19. Trial registration: Clinicaltrials.gov NCT04328493 31/03/2020

scholarly journals Efficacy and safety of nitazoxanide plus atazanavir/ritonavir for the treatment of moderate to severe COVID-19 (NACOVID): A structured summary of a study protocol for a randomised controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Adeniyi Olagunju ◽  
Adeola Fowotade ◽  
Ajibola Olagunoye ◽  
Temitope Olumuyiwa Ojo ◽  
Bolanle Olufunlola Adefuye ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Standard Of Care ◽  
University Teaching ◽  
Chain Reaction ◽  
Open Label ◽  
Link Type ◽  
Care Facilities ◽  
Full Protocol ◽  
Polymerase Chain ◽  
Randomised Controlled

Abstract Objectives To investigate the efficacy and safety of repurposed antiprotozoal and antiretroviral drugs, nitazoxanide and atazanavir/ritonavir, in shortening the time to clinical improvement and achievement of SARS-CoV-2 polymerase chain reaction (PCR) negativity in patients diagnosed with moderate to severe COVID-19. Trial design This is a pilot phase 2, multicentre 2-arm (1:1 ratio) open-label randomised controlled trial. Participants Patients with confirmed COVID-19 diagnosis (defined as SARS-CoV-2 PCR positive nasopharyngeal swab) will be recruited from four participating isolation and treatment centres in Nigeria: two secondary care facilities (Infectious Diseases Hospital, Olodo, Ibadan, Oyo State and Specialist State Hospital, Asubiaro, Osogbo, Osun State) and two tertiary care facilities (Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State and Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State). These facilities have a combined capacity of 146-bed COVID-19 isolation and treatment ward. Inclusion criteria Confirmation of SARS-CoV-2 infection by PCR test within two days before randomisation and initiation of treatment, age bracket of 18 and 75 years, symptomatic, able to understand study information and willingness to participate. Exclusion criteria include the inability to take orally administered medication or food, known hypersensitivity to any of the study drugs, pregnant or lactating, current or recent (within 24 hours of enrolment) treatment with agents with actual or likely antiviral activity against SARS-CoV-2, concurrent use of agents with known or suspected interaction with study drugs, and requiring mechanical ventilation at screening. Intervention and comparator Participants in the intervention group will receive 1000 mg of nitazoxanide twice daily orally and 300/100 mg of atazanvir/ritonavir once daily orally in addition to standard of care while participants in the control group will receive only standard of care. Standard of care will be determined by the physician at the treatment centre in line with the current guidelines for clinical management of COVID-19 in Nigeria. Main outcome measures Main outcome measures are: (1) Time to clinical improvement (defined as time from randomisation to either an improvement of two points on a 10-category ordinal scale (developed by the WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection) or discharge from the hospital, whichever came first); (2) Proportion of participants with SARS-CoV-2 polymerase chain reaction (PCR) negative result at days 2, 4, 6, 7, 14 and 28; (3) Temporal patterns of SARS-CoV-2 viral load on days 2, 4, 6, 7, 14 and 28 quantified by RT-PCR from saliva of patients receiving standard of care alone versus standard of care plus study drugs. Randomisation Allocation of participants to study arm is randomised within each site with a ratio 1:1 based on randomisation sequences generated centrally at Obafemi Awolowo University. The model was implemented in REDCap and includes stratification by age, gender, viral load at diagnosis and presence of relevant comorbidities. Blinding None, this is an open-label trial. Number to be randomised (sample size) 98 patients (49 per arm). Trial status Regulatory approval was issued by the National Agency for Food and Drug Administration and Control on 06 October 2020 (protocol version number is 2.1 dated 06 August 2020). Recruitment started on 9 October 2020 and is anticipated to end before April 2021. Trial registration The trial has been registered on ClinicalTrials.gov (July 7, 2020), with identifier number NCT04459286 and on Pan African Clinical Trials Registry (August 13, 2020), with identifier number PACTR202008855701534. Full protocol The full protocol is attached as an additional file which will be made available on the trial website. In the interest of expediting dissemination of this material, the traditional formatting has been eliminated, and this letter serves as a summary of the key elements in the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

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 T44. 12-MONTH FOLLOW UP OF METABOLIC MEASURES FOLLOWING A RANDOMISED CONTROLLED TRIAL OF TREATMENT OF CLOZAPINE ASSOCIATED OBESITY AND DIABETES WITH EXENATIDE (CODEX)

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S248-S248
Author(s):  
Dan Siskind ◽  
Anthony Russell ◽  
Steve Kisely
Keyword(s):  
Weight Loss ◽  
Fasting Glucose ◽  
Controlled Trial ◽  
Pilot Trial ◽  
Glycated Haemoglobin ◽  
Open Label ◽  
Treatment As Usual ◽  
Obesity And Diabetes ◽  
Randomised Controlled

Abstract Background Clozapine is associated with high rates of obesity and type 2 diabetes (T2DM). Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, can counter clozapine-associated GLP-1 dysregulation. Our randomized, controlled (RCT), open-label, pilot trial of once-weekly extended-release subcutaneous exenatide or treatment as usual (TAU) for 24 weeks (n=28), found 6/14 people on exenatide achieved &gt;5% weight loss vs 1/14 receiving usual care (P = .029). Compared with TAU, participants on exenatide had greater mean weight loss body mass index (BMI) reduction, and reduced fasting glucose and glycated haemoglobin (HbA1c) levels. Methods We followed up CODEX trial participants at 12 months following the end of the trial. We collected information on weight, BMI, waist circumference, blood pressure, fasting glucose, HbA1c, and use of metformin. The primary outcome of interest was change in weight. Change in these parameters from trial baseline to 12 months post endpoint and trial endpoint to 12 months post endpoint was compared between those formerly in the exenatide and TAU arms. Results There were no significant differences between baseline and 12-months post endpoint for any of the variables. Data from endpoint to 12-month follow up point showed significantly greater increases among the former exenatide group compared to the former TAU group for weight, BMI, and proportion with &gt;5% weight gain. Stratifying the dataset by whether participants were on metformin six months after the end of the trial did not alter the overall results. Discussion There were significant increases in weight and BMI in the 12 months post endpoint for the former exenatide group, however there were no significant differences in weight and BMI between baseline and 12-month post endpoint. This is in keeping with other GLP-1RA studies. This information suggests the need for continued use of exenatide among people on clozapine who have achieved weight loss.

scholarly journals Rationale and design of a prospective substudy of clinical endpoint adjudication processes within an investigator-reported randomised controlled trial in patients with coronary artery disease: the GLOBAL LEADERS Adjudication Sub-StudY (GLASSY)

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e026053 ◽  
Author(s):  
Sergio Leonardi ◽  
Anna Franzone ◽  
Raffaele Piccolo ◽  
Eugene McFadden ◽  
Pascal Vranckx ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Academic Research ◽  
Coronary Intervention ◽  
Ethics Committee ◽  
Current Treatment ◽  
Clinical Event ◽  
Open Label ◽  
Standard Regimen ◽  
Randomised Controlled

IntroductionThe GLOBAL LEADERS is an open-label, pragmatic and superiority randomised controlled trial designed to challenge the current treatment paradigm of dual antiplatelet therapy (DAPT) for 12 months followed by aspirin monotherapy among patients undergoing percutaneous coronary intervention. By design, all study endpoints are investigator reported (IR) and not subject to formal adjudication by an independent Clinical Event Committee (CEC), which may introduce detection, reporting or ascertainment bias.Methods and analysisWe designed the GLOBAL LEADERS Adjudication Sub-StudY (GLASSY) to prospectively implement, in a large sample of patients enrolled within the GLOBAL LEADERS trial (7585 of 15 991, 47.5%), an independent adjudication process of reported and unreported potential endpoints, using standardised CEC procedures, in order to assess whether 23-month ticagrelor monotherapy (90 mg twice daily) after 1-month DAPT is non-inferior to a standard regimen of DAPT for 12 months followed by aspirin monotherapy for the primary efficacy endpoint of death, non-fatal myocardial infarction, non-fatal stroke or urgent target vessel revascularisation and superior for the primary safety endpoint of type 3 or 5 bleeding according to the Bleeding Academic Research Consortium criteria.This study will comprehensively assess the comparative safety and efficacy of the two tested antithrombotic strategies on CEC-adjudicated ischaemic and bleeding endpoints and will provide insights into the role of a standardised CEC adjudication process on the interpretation of study findings by quantifying the level of concordance between IR-reported and CEC-adjudicated events.Ethics and disseminationGLASSY has been approved by local ethics committee of all study sites and/or by the central ethics committee for the country depending on country-specific regulations. In all cases, they deemed that it was not necessary to obtain further informed consent from individual subjects.Trial registration numberNCT01813435.

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.

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