Convalescent Plasma and Placebo for the Treatment of COVID-19 Severe Pneumonia

NCT ID: NCT04383535

Last Updated: 2020-09-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

333 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-15

Study Completion Date

2020-09-27

Brief Summary

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A multicenter randomized, double-blind, placebo-controlled clinical trial of Convalescent SARS COVID-19 plasma versus Placebo to evaluate the effect between arms on an ordinal score of six mutually exclusive categories of clinical status at day 30 after study initiation.

Detailed Description

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Introduction

The use of convalescent plasma in the treatment of infectious diseases has been empirically performed for more than a century. It is based upon the assumption that providing exogenous neutralizing antibodies may provide protection while affected patients mount their own immune response. This therapeutic approach appears of particular interest in the context of the current pandemic, in which there is no specific vaccine available nor adequately proven effective pharmacological treatments.

Study purpose, hypothesis and general design

Purpose of the study: evaluate the effectiveness and safety of convalescent plasma in the treatment of SARS-CoV-2 pneumonia (Covid-19) Hypothesis: Convalescent plasma significantly improves the clinical outcome in patients with Covid-19 pneumonia and severity criteria.

Multicenter randomized, double-blind, placebo.controlled clinical trial. Placebo will be a saline solution.

3\. Methodological sustain for including a control arm with placebo Quality evidence about the effectiveness of convalescent plasma in the treatment of Covid-19 pneumonia is not yet available. Although case series and anecdotal reports appear encouraging, the implementation of its use in routine clinical practice requires the validation through controlled clinical trials. In addition the collection, administration and control of plasma is technically demanding and needs a clear support before broadly recommending it. Different scientific institutions and international organisms had clearly suggested to prioritize the application of novel therapeutic techniques with yet unproven efficacy within the context of clinical studies over its empirical use.

On the other hand, for the present study, intervention strategy is proposed in "add-on" modality over the antiviral treatment that each participant may be already receiving, since they represent completely different therapeutic approaches. As such, participation in the present study will not condition the possibility of the participants to receive other treatments, either in intervention or control arms.

4\. Study objectives Primary objective Analyze the difference between arms on an ordinal score of six mutually exclusive categories at day 30 after study initiation. This score includes the following categories

Conditions

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SARS Virus SARS-CoV-2 COVID-19

Keywords

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SARS Virus SARS-CoV-2 COVID-19 Blood Plasma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Multicenter randomized (2:1, 222 plasma 111 placebo), double-blind, placebo-controlled clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
The pharmacist will be unblinded. The study intervention will be covered with an opaque development in order to ensure blinding of the intervention arm.

Study Groups

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Convalescent SARS COVID-19 plasma

Convalescent SARS COVID-19 plasma from a pool of 10 donor plasma, in addition to standard care.

Group Type EXPERIMENTAL

Convalescent SARS COVID-19 plasma

Intervention Type OTHER

Convalescent SARS COVID-19 plasma from a pool of 10 donor plasma. The calculation of the volume to be transfused will be from 10 to 15 ml / kg adjusting the volume to the body weight of each patient, at a suggested infusion rate of 5 to 10 ml / kg / h with an intravenous infusion pump. The infusion rate will be adjusted according to the clinical stability of the patient according to the treating physician.

Placebo

Single infusion of saline solution, in addition to standard care.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Single infusion of saline solution, in addition to standard care. The calculation of the volume to be transfused will be from 10 to 15 ml / kg adjusting the volume to the body weight of each patient, at a suggested infusion rate of 5 to 10 ml / kg / h with an intravenous infusion pump. The infusion rate will be adjusted according to the clinical stability of the patient according to the treating physician.

Interventions

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Convalescent SARS COVID-19 plasma

Convalescent SARS COVID-19 plasma from a pool of 10 donor plasma. The calculation of the volume to be transfused will be from 10 to 15 ml / kg adjusting the volume to the body weight of each patient, at a suggested infusion rate of 5 to 10 ml / kg / h with an intravenous infusion pump. The infusion rate will be adjusted according to the clinical stability of the patient according to the treating physician.

Intervention Type OTHER

Placebo

Single infusion of saline solution, in addition to standard care. The calculation of the volume to be transfused will be from 10 to 15 ml / kg adjusting the volume to the body weight of each patient, at a suggested infusion rate of 5 to 10 ml / kg / h with an intravenous infusion pump. The infusion rate will be adjusted according to the clinical stability of the patient according to the treating physician.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Confirmed diagnosis of Covid-19 through qualitative polymerase-reverse transcriptase (qRT-PCR -GeneDX Co, Ltd o similar).
* Imagining-diagnosed pneumonia (Rx or CT scan).
* MSOFA score (Modified SOFA) of 2 or more (modified organic failure assessment)
* Informed consent.

Exclusion Criteria

* Pregnant women
* Women at reproductive age not willing to avoid unprotected sexual intercourse up to Day 30 after study initiation.
* Women in the breastfeeding period
* Patients receiving experimental treatments under development within 30 days prior to study initiation.
* Patients with a previous history of allergic reactions to blood or blood-components transfusion.
* Diagnosis or clinical suspicion of an alternative microbiological cause for pneumonia besides COVID-19
* Use of systemic corticosteroids within 15 days prior to entering the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Italiano de Buenos Aires

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nora A Fuentes, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Privado de la Comunidad de Mar del Plata

Florencia Otermin, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Italiano de la Plata

Esteban Nannini, MD

Role: PRINCIPAL_INVESTIGATOR

Sanatorio Britanico Rosario, pcia Santa Fe

Karina Rainiero, MD

Role: PRINCIPAL_INVESTIGATOR

Suiza Argentina

Erica Miyazaki, MD

Role: PRINCIPAL_INVESTIGATOR

Clinica Zabala

Gabriela Vidiella, MD

Role: PRINCIPAL_INVESTIGATOR

Sanatorio Agote

Wanda Cornistein, MD

Role: PRINCIPAL_INVESTIGATOR

Austral University, Argentina

Leandro Burgos, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Italiano de Buenos Aires

Locations

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Hospital Italiano de Buenos Aires

Ciudad Autonoma de Buenos Aire, Buenos Aires F.D., Argentina

Site Status

Countries

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Argentina

References

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Maiztegui JI, Fernandez NJ, de Damilano AJ. Efficacy of immune plasma in treatment of Argentine haemorrhagic fever and association between treatment and a late neurological syndrome. Lancet. 1979 Dec 8;2(8154):1216-7. doi: 10.1016/s0140-6736(79)92335-3.

Reference Type BACKGROUND
PMID: 92624 (View on PubMed)

Tanne JH. Covid-19: FDA approves use of convalescent plasma to treat critically ill patients. BMJ. 2020 Mar 26;368:m1256. doi: 10.1136/bmj.m1256. No abstract available.

Reference Type BACKGROUND
PMID: 32217555 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32219428 (View on PubMed)

Roback JD, Guarner J. Convalescent Plasma to Treat COVID-19: Possibilities and Challenges. JAMA. 2020 Apr 28;323(16):1561-1562. doi: 10.1001/jama.2020.4940. No abstract available.

Reference Type BACKGROUND
PMID: 32219429 (View on PubMed)

Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, Chan P, Wong KC, Leung CB, Cheng G. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005 Jan;24(1):44-6. doi: 10.1007/s10096-004-1271-9.

Reference Type BACKGROUND
PMID: 15616839 (View on PubMed)

Kalil AC. Treating COVID-19-Off-Label Drug Use, Compassionate Use, and Randomized Clinical Trials During Pandemics. JAMA. 2020 May 19;323(19):1897-1898. doi: 10.1001/jama.2020.4742. No abstract available.

Reference Type BACKGROUND
PMID: 32208486 (View on PubMed)

Angus DC. Optimizing the Trade-off Between Learning and Doing in a Pandemic. JAMA. 2020 May 19;323(19):1895-1896. doi: 10.1001/jama.2020.4984. No abstract available.

Reference Type BACKGROUND
PMID: 32227198 (View on PubMed)

Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med. 2006 Oct 17;145(8):599-609. doi: 10.7326/0003-4819-145-8-200610170-00139. Epub 2006 Aug 29.

Reference Type RESULT
PMID: 16940336 (View on PubMed)

Iannizzi C, Chai KL, Piechotta V, Valk SJ, Kimber C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Jindal A, Cryns N, Estcourt LJ, Kreuzberger N, Skoetz N. Convalescent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2023 May 10;5(5):CD013600. doi: 10.1002/14651858.CD013600.pub6.

Reference Type DERIVED
PMID: 37162745 (View on PubMed)

Iannizzi C, Chai KL, Piechotta V, Valk SJ, Kimber C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Jindal A, Cryns N, Estcourt LJ, Kreuzberger N, Skoetz N. Convalescent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2023 Feb 1;2(2):CD013600. doi: 10.1002/14651858.CD013600.pub5.

Reference Type DERIVED
PMID: 36734509 (View on PubMed)

Piechotta V, Iannizzi C, Chai KL, Valk SJ, Kimber C, Dorando E, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Estcourt LJ, Skoetz N. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 May 20;5(5):CD013600. doi: 10.1002/14651858.CD013600.pub4.

Reference Type DERIVED
PMID: 34013969 (View on PubMed)

Simonovich VA, Burgos Pratx LD, Scibona P, Beruto MV, Vallone MG, Vazquez C, Savoy N, Giunta DH, Perez LG, Sanchez MDL, Gamarnik AV, Ojeda DS, Santoro DM, Camino PJ, Antelo S, Rainero K, Vidiella GP, Miyazaki EA, Cornistein W, Trabadelo OA, Ross FM, Spotti M, Funtowicz G, Scordo WE, Losso MH, Ferniot I, Pardo PE, Rodriguez E, Rucci P, Pasquali J, Fuentes NA, Esperatti M, Speroni GA, Nannini EC, Matteaccio A, Michelangelo HG, Follmann D, Lane HC, Belloso WH; PlasmAr Study Group. A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia. N Engl J Med. 2021 Feb 18;384(7):619-629. doi: 10.1056/NEJMoa2031304. Epub 2020 Nov 24.

Reference Type DERIVED
PMID: 33232588 (View on PubMed)

Other Identifiers

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5565

Identifier Type: -

Identifier Source: org_study_id