Convalescent Plasma Treatment in COVID-19

NCT04476888 | Completed DMC

• 1 other identifier: CON000000000880
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred initially in December 2019 in the city of Wuhan, Hubei province, China. Patients mainly presented with respiratory symptoms and this novel pathogen was identified.At present, the core management of COVID-19 includes infection prevention, case detection, monitoring, and supportive care. While specific new drugs and vaccines are being researched, certain drugs that are already present in medical arsenal are under trial too. One investigational treatment being explored for COVID-19 is the use of convalescent plasma (CP) collected from recovered COVID-19 patients. Convalescent Plasma is a source of passive immune therapy- the administration of specific antibodies against a given agent for preventing or treating an infectious disease due to that agent. The main anticipated mechanism of action of Convalescent Plasma therapy in COVID19 is viral neutralization. Other possible mechanisms include antibody-dependent cellular cytotoxicity and phagocytosis. There are numerous examples in which convalescent plasma (CP) has been used successfully as post exposure prophylaxis and/or treatment of infectious diseases, including other outbreaks of coronaviruses e.g. SARS-1, MERS-CoV and very recently in 2014, the Ebola virus outbreak. In SARS-CoV-2, Shen et al published a case series of 5 critically ill patients with COVID-19 and acute respiratory distress syndrome showing improvement in clinical status after transfusion of CP. Therefore, the objective of this study is to determine the safety and efficacy of transfusing convalescent plasma in patients admitted with COVID-19 at Aga Khan University Karachi, Pakistan. The investigators hypothesize that CP will decrease the length of hospital stay and overall mortality in patients with COVID-19. In this study, convalescent plasma will be collected from the donors who have been recovered from SARS-CoV-2 infection and transfused it to the patients admitted with active severe /critical COVID-19 at the Aga Khan University Hospital Karachi. STUDY DESIGN: Non-randomized open Label trial INCLUSION CRITERIA IN TREATMENT ARM: i. Inpatients at AKU with positive SARS-CoV-2 infection by rRT-PCR and who have provided written informed consent for inclusion in the trial; ii. Age ≥ 18 years; iii. Severe or immediately life-threatening COVID-19 defined by any of:

• Respiratory rate ≥ 30/min;
• Blood oxygen saturation ≤ 93% at room air;
• Partial pressure of arterial Oxygen to Fraction of inspired Oxygen ratio \< 300;
• Lung infiltrates \> 50% within 24 to 48 hours on radiology ( X-ray or CT scan);
• Need for mechanical ventilation.
• respiratory failure
• septic shock
• multiple organ dysfunction or failure EXCLUSION CRITERIA: i. Negative rRT-PCR from respiratory secretions or blood within 48 h prior to assessment of eligibility. ii. History of allergic reaction to blood or plasma products (as judged by the investigator). iii. Medical conditions in which receipt of 500 mL intravascular volume may be detrimental to the patient (e.g., actively decompensated congestive heart failure). iv. Enrolment in any other clinical trial for an investigational therapy. CONTROL GROUP: COVID-19 patients recruited during the period before CP becomes available or for whom no compatible CP is available will be given Standard of Care and will be followed for study outcomes. Data from these SC patients will be used as comparator in the analysis of the study.

Conditions

Covid19

Keywords

Convalescent plasma; Covid 19

Outcome Measures

Primary Outcomes (3)

• Decrease length of stay

  Decrease length of stay in hospital , Decrease length of stay in ICU/special care unit

  From date on which intervention given until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 1 month

• Overall mortality

  Status alive or death

  From date on which intervention given until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 1 month

• Incidence of adverse events related to Convalescent Plasma transfusion

  Any adverse event after the transfusion of Convalescent plasma which include TRALI, TACO, allergic reaction, anaphylaxis.

  After receiving intervention (CP) till 24 hours

Secondary Outcomes (7)

• Ordinal scale

  From date on which intervention given until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 1 month

• Improvement in Laboratory Parameters: Serum Ferritin

  From date on which intervention given until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 1 month

• Improvement in Laboratory Parameters: Procalcitonin

  From date on which intervention given until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 1 month

• Improvement in Laboratory Parameters: C-Reactive Protein

  From date on which intervention given until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 1 month

• Improvement in Laboratory Parameters: D-Dimer

  From date on which intervention given until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 1 month

Study Arms (2)

Treatment arm/CP recipient

EXPERIMENTAL

Patients with severe/critical COVID 19 who will receive 500 ml of Convalescent plasma (CP), obtained from donors who have been recovered from SARS-CoV-2 infection. These patients may or may not get other treatment modalities e.g. steroids,Tocilizumab, Azithromycin etc

Biological: Convalescent Plasma (CP); Other: Drugs and supportive care

Control arm

OTHER

Patients with severe/critical COVID 19 who will not receive Convalescent plasma (CP). These will be those who were recruited during the period before CP becomes available or for whom no compatible CP is available. These patients will receive one or more of the other treatment modalities e.g. steroids,Tocilizumab, Azithromycin etc

Other: Drugs and supportive care

Interventions

Convalescent Plasma (CP) BIOLOGICAL

500 ml of Convalescent plasma in a single dose will be transfused over a period of 1- 2 hours.

Treatment arm/CP recipient

Drugs and supportive care OTHER

This will include drugs like steroids, tocilizumab, azithromycin and supportive care

Control arm; Treatment arm/CP recipient

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ii. Age ≥ 18 years;
• iii. Severe or immediately life-threatening COVID-19 defined by any of:
• Respiratory rate ≥ 30/min;
• Blood oxygen saturation ≤ 93% at room air;
• Partial pressure of arterial Oxygen to Fraction of inspired Oxygen ratio \< 300;
• Lung infiltrates \> 50% within 24 to 48 hours on radiology ( X-ray or CT scan);
• Need for mechanical ventilation.
• respiratory failure
• septic shock
• multiple organ dysfunction or failure

You may not qualify if:

• i. Negative rRT-PCR from respiratory secretions or blood within 48 h prior to assessment of eligibility.
• ii. History of allergic reaction to blood or plasma products (as judged by the investigator).
• iii. Medical conditions in which receipt of 500 mL intravascular volume may be detrimental to the patient (e.g., actively decompensated congestive heart failure).
• iv. Enrollment in any other clinical trial for an investigational therapy

Sponsors & Collaborators

• Aga Khan University: lead

Study Sites (1)

Aga Khan University Hospital

Karachi, Sindh, Pakistan

Location

Related Publications (4)

• Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, Liu R, Watt CL, Chan WM, Lai KY, Koo CK, Buckley T, Chow FL, Wong KK, Chan HS, Ching CK, Tang BS, Lau CC, Li IW, Liu SH, Chan KH, Lin CK, Yuen KY. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011 Feb 15;52(4):447-56. doi: 10.1093/cid/ciq106. Epub 2011 Jan 19.

  PMID: 21248066 BACKGROUND

• Arabi Y, Balkhy H, Hajeer AH, Bouchama A, Hayden FG, Al-Omari A, Al-Hameed FM, Taha Y, Shindo N, Whitehead J, Merson L, AlJohani S, Al-Khairy K, Carson G, Luke TC, Hensley L, Al-Dawood A, Al-Qahtani S, Modjarrad K, Sadat M, Rohde G, Leport C, Fowler R. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus. 2015 Nov 19;4:709. doi: 10.1186/s40064-015-1490-9. eCollection 2015.

  PMID: 26618098 BACKGROUND

• Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Apr 28;323(16):1582-1589. doi: 10.1001/jama.2020.4783.

  PMID: 32219428 BACKGROUND

• Robbins JB, Schneerson R, Szu SC. Perspective: hypothesis: serum IgG antibody is sufficient to confer protection against infectious diseases by inactivating the inoculum. J Infect Dis. 1995 Jun;171(6):1387-98. doi: 10.1093/infdis/171.6.1387.

  PMID: 7769272 BACKGROUND

MeSH Terms

Conditions

COVID-19

Interventions

Pharmaceutical Preparations; Palliative Care

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Muhammad Hasan, MBBS, FCPS

  Aga Khan University Hospital, Karachi

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Instructor

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: July 20, 2020
• Study Start: April 26, 2020
• Primary Completion: September 15, 2020
• Study Completion: October 10, 2020
• Last Updated: January 20, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)