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

NCT04383535 | Completed DMC

• 1 other identifier: 5565
• Study Type: interventional
• Target: 333
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

SARS Virus; SARS-CoV-2; COVID-19

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Clinical status during follow-up at 30th day

  Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

  30th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Secondary Outcomes (13)

• Clinical status during follow-up at 7th day

  7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

• Clinical status during follow-up at 14th day

  14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

• Time until hospital discharge (days).

  Whenever the patient is discharge from the hospital or die without discharge, through study completion, an average of 14 days from admission

• Time until discharge from ICU (days)

  Whenever the patient is discharge from ICU or die in ICU, through study completion, an average of 10 days from admission

• Time to death

  In a 30 days follow up period

Study Arms (2)

Convalescent SARS COVID-19 plasma

EXPERIMENTAL

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

Other: Convalescent SARS COVID-19 plasma

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Convalescent SARS COVID-19 plasma 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.

Convalescent SARS COVID-19 plasma

Placebo 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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital Italiano de Buenos Aires: lead

Study Sites (1)

Hospital Italiano de Buenos Aires

Ciudad Autonoma de Buenos Aire, Buenos Aires F.D., 1181, Argentina

Location

Related Publications (12)

• 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.

  PMID: 92624 BACKGROUND

• 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.

  PMID: 32217555 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

• 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.

  PMID: 32219429 BACKGROUND

• 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.

  PMID: 15616839 BACKGROUND

• 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.

  PMID: 32208486 BACKGROUND

• 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.

  PMID: 32227198 BACKGROUND

• 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.

  PMID: 16940336 RESULT

• 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.

  PMID: 37162745 DERIVED

• 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.

  PMID: 36734509 DERIVED

• 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.

  PMID: 34013969 DERIVED

• 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.

  PMID: 33232588 DERIVED

MeSH Terms

Conditions

Severe Acute Respiratory Syndrome; COVID-19

Interventions

COVID-19 Serotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Nora A Fuentes, MD

  Hospital Privado de la Comunidad de Mar del Plata

  PRINCIPAL INVESTIGATOR

• Florencia Otermin, MD

  Hospital Italiano de la Plata

  PRINCIPAL INVESTIGATOR

• Esteban Nannini, MD

  Sanatorio Britanico Rosario, pcia Santa Fe

  PRINCIPAL INVESTIGATOR

• Karina Rainiero, MD

  Suiza Argentina

  PRINCIPAL INVESTIGATOR

• Erica Miyazaki, MD

  Clinica Zabala

  PRINCIPAL INVESTIGATOR

• Gabriela Vidiella, MD

  Sanatorio Agote

  PRINCIPAL INVESTIGATOR

• Wanda Cornistein, MD

  Austral University, Argentina

  PRINCIPAL INVESTIGATOR

• Leandro Burgos, MD

  Hospital Italiano de Buenos Aires

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The pharmacist will be unblinded. The study intervention will be covered with an opaque development in order to ensure blinding of the intervention arm.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter randomized (2:1, 222 plasma 111 placebo), double-blind, placebo-controlled clinical trial

Study Record Dates

• First Submitted: May 6, 2020
• First Posted: May 12, 2020
• Study Start: May 15, 2020
• Primary Completion: September 27, 2020
• Study Completion: September 27, 2020
• Last Updated: September 30, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

AR (1)