A Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications

Phase 2

Not yet recruiting

Conditions: Coronavirus as the cause of diseases classified elsewhere,

Registration Number: CTRI/2020/04/024915

Lead Sponsor: Max Super Speciality Hospital A Unit of Devki Devi Foundation

Brief Summary: The novel coronavirus disease (COVID-19),which began in Wuhan, China, in December 2019, has been declared to be apandemic by the World Health Organization (WHO), Caused by the severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2), COVID-19 has resulted in 1,781,127 casesand 108,994 deaths globally (till 12th April, 2020), affecting 199 countriesand 2 international conveyances. US FDA has recently approved ConvalescentPlasma from patients recovered from COVID 19 for the treatment of severe orlife threatening COVID-19 infections. In a small case series, five criticallyill COVID-19 patients with ARDS were treated with convalescent plasmacontaining neutralizing antibodies. Infusion of plasma was followed byimprovement in clinical status in all five patients, with no deaths and thestudy reported that three patients were discharged, whilst two continued to bestable on mechanical ventilation. We designed this phase II, open label,randomized clinical trial with the primary objective to assess the safety andefficacy of the therapy in the second stage.

Thestudy will be conducted over the period of one year on 100 Hospitalized,COVID-19 patients, fulfill the inclusion and exclusion criteria, and areadmitted for care at COVID-19 management facilities in Max healthcare Hospitalwill be eligible for inclusion in the trial. This PhaseII, open label, randomized controlled trial. Consecutive patients meeting theinclusionâ€“exclusion criteria and providing informed consent will be randomlyassigned to the test and the control group using random numbers generated byrandomization.com. Patients in the test group will receive convalescent plasmaand the control group will be on standard care.

COVID-19 convalescent plasma will be collected from recovered individuals if they are eligible to donate blood. Forinfusion of plasma existing SOP of the wards w.r.t transfusion of FFP should befollowed with special care to monitor these patients during and post-24 hoursof transfusion. AnABO compatible plasma bag of approx. 200ml will be issued maintaining all theblood bank records after thawing at 37 degree Celsius. The first plasmatransfusion may be followed by one or two additional doses of 200 ml at 24hours interval according to disease severity and tolerance of the infusions.

Baseline data about the demography, clinical presentations, ongoing medical therapy, and clinical history of participants in both arms will be collected and compared. Response to convalescent plasma will be coded as a binary outcome â€“ based on whether the composite primary end point is met or not. Adverse events associated with infusion of convalescent plasma will also be descriptively summarized and compared with the adverse events experienced by participants receiving standard of care.

Eligibilityof Potential Donor

1.Only males and nulliparous female donors of weight > 55 kgs willbe included.

2.Donor eligibility criteria for whole blood donation as per the departmental SOPwill be followed in accordance to the Drugs & Cosmetics Act 1940 and rules1945 therein (as amended till March 2020). Donor will be screened, followedby brief physical examination.

3.Donors not fit to donate blood based on the history and examination will bedeferred and excluded from plasma donor pool for a time period specified bycountry regulation & departmental SOPs.

4. Inaddition to the aforementioned donor eligibility criteria, two EDTA samples (5ml each) and one plain sample (5 ml) will be drawn for the followingpre-donation tests as required for convalescent plasmapheresis (CPP).

â€¢ Blood group and antibody screening â€“ Antibodyscreen positive donors will be deferred.

â€¢ Complete blood count including Hb,Hct,Platelet count, Total and differential leucocyte count. Donors with Hb>12.5g/dl,platelet count >1, 50,000 per microliter of blood and TLC within normallimits will be accepted.

â€¢ Screening for HIV, HBV and HCV by serology andNAT. Donor negative by both the tests will be included.

â€¢ Screening for syphilis and malaria byserology. Negative donors will be included

â€¢ Total serum protein. Donors with total serumprotein > 6gm/dl will be accepted (as per Drugs and Cosmetics (SecondAmendment) Rules, 2020)

â€¢ Titration of anti-COVID-19 (both IgG and IgM)antibodies and SARS- CoV-2 neutralizing antibodies may be done depending onavailability of facilities at the time of testing. (Desired titers for IgGantibodies >1024 or neutralizing antibodies >40) doubling dilution ofdonor serum will be done and titration will be done using ELISA. If not done atthe time of plasma collection the donor samples will be stored in aliquots at<-80Â° C to be tested at a later date.

â€¢ Molecular test for COVID-19 either fromnasopharyngeal swab specimens or blood may be done depending on availability oftests. Donors positive will be deferred.

Detailed Description: Not available

Recruitment & Eligibility

Status: Not Yet Recruiting

Sex: All

Target Recruitment: 100

Inclusion Criteria

Patients admitted with RT-PCR confirmed COVID-19 illness.
Age > 18 years 3.
Written informed consent 4.
Has any of the two a.
PaO2/ FiO2 <300 b.
Respiratory Rate > 24/min and SaO2 < 93% on room air.

Exclusion Criteria

Pregnant women 2.
Breastfeeding women 3.
Known hypersensitivity to blood products 4.
Receipt of Pooled Immunoglobulin in last 30 days 6.
Participating in any other clinical trial 7.
Clinical status precluding infusion of blood products.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary outcome is a composite measure of the avoidance of -	one year
1. Progression to severe ARDS (P/F ratio 100) and	one year
2. All-cause Mortality at 28 days	one year

Secondary Outcome Measures

Name	Time	Method
1. Time to symptom resolution-Fever,Shortness of Breath,Fatigue	2. Hospital length of stay

Trial Locations

Locations (1): Max Super Speciality hospital, Saket (A unit of Devki Devi Foundation)
🇮🇳
Delhi, DELHI, India
Max Super Speciality hospital, Saket (A unit of Devki Devi Foundation)
🇮🇳Delhi, DELHI, India
Dr Sangeeta Pathak
Principal investigator
9873081647
sangeeta.pathak@maxhealthcare.com