Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Convalescent Plasma Therapy in Severe COVID-19 Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04403477
Recruitment Status : Recruiting
First Posted : May 27, 2020
Last Update Posted : May 27, 2020
Sponsor:
Collaborator:
Dhaka Medical College
Information provided by (Responsible Party):
Fazle Rabbi Chowdhury, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Brief Summary:

As of March 18, 2020, COVID-19 cases were reported in approximately 195 countries. No specific therapeutic agents or vaccines for COVID-19 are available. Several therapies, such as remdesivir and favipiravir, are under investigation, but the antiviral efficacy of these drugs is not yet known. The use of convalescent plasma (CP) was recommended as an empirical treatment during outbreaks of Ebola virus in 2014. A protocol for treatment of Middle East respiratory syndrome coronavirus (MERS-CoV) with CP was established in 2015. This approach with other viral infections such as SARS-CoV, H5N1 avian influenza, and H1N1 influenza also suggested that transfusion of CP was effective. In previous reports, most of the patients received the CP by single transfusion. In a study involving patients with pandemic influenza A(H1N1) 2009 virus infection, treatment of severe infection with CP (n = 20 patients) was associated with reduced respiratory tract viral load, serum cytokine response, and mortality. In another study involving 80 patients with SARS, the administration of CP was associated with a higher rate of hospital discharge at day 22 from symptom onset compared with patients who did not receive CP. Accordingly, these findings raise the hypothesis that use of CP transfusion could be beneficial in patients infected with SARS-CoV-2. The objective of this study is to describe the initial clinical experience with CP transfusion administered to severe COVID-19 patients. The primary endpoint of this trial would be to assess the tolerability, efficacy, and dose-response of CP in severe COVID-19 patients. The secondary endpoint would be to assess the clinical and laboratory parameters after therapy, in-hospital mortality, length of hospital stay, reduction in the proportion of deaths, length of ICU stay, requirement of ventilator and duration of ventilator support. All RT-PCR positive cases with features of severe infection will be enrolled in this study. Apheretic CP will be collected from a recovered patient (consecutive two RT-PCR samples negative) between day 22 to 35 days of recovery and those with the antibody titre above 1:320.

This RCT will consist of three arms, a. standard care, b. standard care and 200 ml CP and c. standard care and 400 ml CP as a single transfusion. Twenty (20) patients will be enrolled for each arm. Randomization will be done by someone not associated with the care or assessment of the patients by means of a random number table. Allocations will be concealed in sequentially numbered, opaque, sealed envelopes. Clinical parameters [fever, cough, dyspnea, respiratory rate, PaO2/ FiO2 level, pulse, BP, the requirement of O2, and others] will be recorded before and after CP. Laboratory parameters such as complete blood count, CRP, chest X-ray, SGPT, SGOT, S. Ferritin, and serum antibody titre will be measured before and after transfusion. Allergic or serum sickness-like reactions will be noted and adjusted with outcome. Laboratory tests including RT-PCR will be done at BSMMU virology and laboratory medicine department. Apheretic plasma will be collected at the transfusion medicine department of SHNIBPS hospital, ELISA, antibody titre will be done at CMBT, and patients will be enrolled at DMC and MuMCH. All necessary screening tests will be done before transfusion.

Graphpad Prism v 7.0 will be used for analysis. One way ANOVA test, a non-parametric Mann-Whitney test, and a Kruskal-Wallis test will be performed to compare the arms. For parametric outcomes, the investigators will compare the odds ratios across the pairs.


Condition or disease Intervention/treatment Phase
Covid19 Convalescence Biological: Convalescent plasma Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Arm-A: Standard supportive treatment; Arm-B: Standard supportive treatment + CP 200 ml; Arm C: Standard supportive treatment + CP 400 ml
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Convalescent Plasma Transfusion Therapy in Severe COVID-19 Patients- a Tolerability, Efficacy and Dose-response Phase II RCT
Actual Study Start Date : May 20, 2020
Estimated Primary Completion Date : July 20, 2020
Estimated Study Completion Date : October 30, 2020

Arm Intervention/treatment
No Intervention: Standard treatment
Standard supportive treatment (Oxygen, Enoxaparine, antibiotic, fluid, immune modulator (Steroid) and or antiviral (favipiravir or ramdesivir or lopinavir + ritonavir)
Experimental: Standard treatment + 200 ml plasma
Standard supportive treatment + 200 ml apheretic convalescent plasma single transfusion
Biological: Convalescent plasma
Apheretic convalescent plasma from a COVID-19 survivor
Other Name: Plasma therapy

Experimental: Standard treatment + 400 ml plasma
Standard supportive treatment + 400 ml apheretic convalescent plasma single transfusion
Biological: Convalescent plasma
Apheretic convalescent plasma from a COVID-19 survivor
Other Name: Plasma therapy




Primary Outcome Measures :
  1. Proportion of In-hospital mortality [ Time Frame: 7 days ]
    % of patients died after enrolment

  2. Time to death [ Time Frame: 7 days ]
    Time to death in hours after enrolment


Secondary Outcome Measures :
  1. Fever [ Time Frame: 7 days ]
    Temperature in degree Fahrenheit at Day 0, 1, 3, 7

  2. Respiratory distress [ Time Frame: 7 days ]
    Respiratory rate per minute at Day 0, 1, 3, 7

  3. Saturation of oxygen [ Time Frame: 7 days ]
    Saturation of oxygen in % at Day 0, 1, 3, 7

  4. Blood pressure [ Time Frame: 7 days ]
    Blood pressure in mm of Hg at Day 0, 1, 3, 7

  5. Oxygen requirement [ Time Frame: 7 days ]
    Oxygen requirements in liter/min at Day 0, 1, 3, 7

  6. C-reactive Protein [ Time Frame: Day 0, 3 and 7 ]
    CRP level in mg/litre

  7. Ferritin [ Time Frame: Day 0, 3 and 7 ]
    Serum Ferritin level in ng/ml

  8. SGPT [ Time Frame: Day 0, 3 and 7 ]
    Serum SGPT level in I/U

  9. SGOT [ Time Frame: Day 0, 3 and 7 ]
    Serum SGOT level in I/U

  10. ICU stay [ Time Frame: 14 days ]
    Duration of ICU stay in days

  11. Ventilator support [ Time Frame: 14 days ]
    Requirement of ventilator support in hours

  12. Hospital stay [ Time Frame: 14 days ]
    Duration of hospital stay in days

  13. Proportion of Transfusion reaction [ Time Frame: 24 hours ]
    % of patients developed early transfusion reaction like fever, sweating, rash, abdominal pain, urticaria, vomiting, wheezing, chest tightness and hypotension



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Respiratory rate > 30 breaths/min; PLUS
  2. Severe respiratory distress; or SpO2 ≤ 88% on room air or PaO2/FiO2≤ 300 mm of Hg, PLUS
  3. Radiological evidence of bilateral lung infiltrate, AND OR
  4. Systolic BP < 90 mm of Hg or diastolic BP <60 mm of Hg. AND OR
  5. Criteria 1 to 4 AND or patient in Ventilator support

Exclusion Criteria:

  1. Patients below18 years.
  2. Pregnant women and breast-feeding mothers.
  3. Previous history of allergic reaction to plasma
  4. Those who will not give consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04403477


Contacts
Layout table for location contacts
Contact: Mohammad S Rahman, MPhil,FCPS +88 01971840757 srkhasru@gmail.com
Contact: Fazle R Chowdhury, FCPS; PhD +88 01916578699 mastershakil@hotmail.com

Locations
Layout table for location information
Bangladesh
Bangabandhu Sheikh Mujib Medical University Recruiting
Dhaka, Bangladesh, 1200
Contact: Sayedur Rahman, MPhil; FCPS    +88 01971840757    srkhasru@gmail.com   
Contact: Fazle R Chowdhury, FCPS;PhD    +88 01916578699    mastershakil@hotmail.com   
Sponsors and Collaborators
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
Dhaka Medical College
Investigators
Layout table for investigator information
Study Chair: Mohammad S Rahman, MPhil; FCPS Professor and Chairman of Pharmacology, BSMMU
Layout table for additonal information
Responsible Party: Fazle Rabbi Chowdhury, Assistant Professor, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
ClinicalTrials.gov Identifier: NCT04403477    
Other Study ID Numbers: BSMMU/2020/6104
First Posted: May 27, 2020    Key Record Dates
Last Update Posted: May 27, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be shared with the journal authority and make public as part of the publication
Supporting Materials: Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: six months
Access Criteria: Available on public domain like figshare, researchgate and others

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Convalescence
Disease Attributes
Pathologic Processes