NCT04479163

Prevention of Severe Covid-19 in Infected Elderly by Early Administration of Convalescent Plasma With High-titers of Antibody Against SARS-CoV2

Completed NA Last updated 22 December 2020

What this trial tests

NA trial testing Convalescent Plasma in COVID in 165 participants. Completed in 25 October 2020.

Timeline

4 June 2020

Primary endpoint
25 October 2020

25 October 2020

Quick facts

Lead sponsor	Fundacion Infant
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	prevention
Enrollment	165
Start date	4 June 2020
Primary completion	25 October 2020
Estimated completion	25 October 2020
Sites	11 locations across Argentina

Drugs / interventions tested

• Convalescent Plasma — full drug profile →
• Placebo

Conditions studied

• COVID — all drugs for COVID →

Sponsor

Fundacion Infant

Who can join

65 and older, any sex, with COVID. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Trial design. Randomized, double-blind, placebo-controlled trial in a catchment population of 2,020,860 age-appropriate subjects in the state of Buenos Aires and 235,000 in the city of Buenos Aires.

Institutions. Hospitals San Juan de Dios, Simplemente Evita, Dr. Carlos Bocalandro, Evita Pueblo, Sanatorio Antartida, Hospital Central de San Isidro, Clinica Olivos in the state of Buenos Aires with 38 regional and town hospitals acting as referral centers, and Hospital Militar Central, Sanatorio de Los Arcos, Hospital Universitario CEMIC, Sanatorio Sagrado Corazon, Sanatorio Finochietto, Sanatorio Anchorena, Centro Gallego, and in the city of Buenos Aires in Argentina.

Study population. Subjects \>= 75 years of age irrespective of presenting comorbidities or between 65-74 years of age with at least one comorbidity (hypertension, diabetes, obesity, chronic renal failure, and COPD) who experience the following signs and symptoms for less than 48 hours at the time of screening for SARS CoV2 by RT-PCR: (a) a temperature \>=37.5°C and/or unexplained sweating and/or chills and (b) at least one of the following: dry cough, dyspnea, fatigue, myalgia, anorexia, sore throat, loss of taste and/or smell, rhinorrhea. Subjects consenting to screening will be tested by reverse-transcriptase-polymerase-chain-reaction (RT-PCR) for SARS-CoV-2 in a nasopharyngeal and an oropharyngeal swab and invited to participate when RNA for the virus is detected.

Intervention. Eligible, consenting patients will be randomized using an electronic system to receive 250 ml of convalescent plasma with an IgG titer against SARS-CoV2 spike (S) protein \>1:1,000 (COVIDAR IgG, Insituto Leloir, Argentina) or placebo (normal saline 0.9%) administered in a 1:1 ratio. Both treatment and placebo will be concealed using dark bags and tape to cover the infusion line. Treatment will be administered \<72 hours from initiation of symptoms. Subjects will be monitored for 12 hours after treatment for adverse events.

Clinical and laboratory monitoring. All participating subjects will be admitted to the hospital upon enrollment. Twenty-four hours after completing the infusion, a sample of venous blood (5 ml) will be obtained from all participants to measure anti-S IgG SARS-CoV2 in serum (COVIDAR IgG, Leloir) and preserved at -20°C until completion of the study. Patient evolution will be assessed daily by study physicians during hospitalization until day 25 and/or at home until day 15, in the event of earlier discharge from the hospital. Study physicians will use predesigned questionnaires to collect clinical information. An Independent Data Safety Monitoring Board (DSMB) will supervise participating subjects during the study.

Endpoints. The primary endpoint of the trial is development of severe respiratory disease defined as a respiratory rate (RR)\>30 and/or an O2 sat\<93% when breathing room air determined using a predefined protocol. Three other clinical endpoints include (a) life threatening respiratory disease, defined as need for 100% oxygen supplementation and/or non-invasive or invasive ventilation and/or admission to intensive care; (b) critical systemic illness, defined as respiratory failure (PaO2/FiO2 ≤ 200 mm Hg) and/or shock and/or multiorganic distress syndrome; and (c) death.

Statistical analysis. The study is designed to have one interim analysis when the outcome results for 50% of the subjects is obtained. The minimally clinically important difference was set at a 40% relative reduction for an expected outcome rate of 50% in the control group reduced to 30% in the intervention group. A total sample size of 210 subjects (105 per trial arm) was estimated to have 80% power at a significance level (alpha) of 0.05 using a two-sided z-test with continuity correction.

Ethical considerations. The trial has been approved by the institutional review boards of participating institutions and the Central Ethics Committee of the state of Buenos Aires. The study will be conducted in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonization. Written informed consent will be obtained from all patients for screening and enrollment.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults.
   Libster R, Pérez Marc G, Wappner D, Coviello S, et al · · 2021 · cited 726× · PMID 33406353 · DOI 10.1056/nejmoa2033700
2. Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis.
   Janiaud P, Axfors C, Schmitt AM, Gloy V, et al · · 2021 · cited 189× · PMID 33635310 · DOI 10.1001/jama.2021.2747
3. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review.
   Piechotta V, Iannizzi C, Chai KL, Valk SJ, et al · · 2021 · cited 106× · PMID 34013969 · DOI 10.1002/14651858.cd013600.pub4
4. COVID-19 Convalescent Plasma and Clinical Trials: Understanding Conflicting Outcomes.
   Focosi D, Franchini M, Pirofski LA, Burnouf T, et al · · 2022 · cited 79× · PMID 35262370 · DOI 10.1128/cmr.00200-21
5. Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.
   Axfors C, Janiaud P, Schmitt AM, Van't Hooft J, et al · · 2021 · cited 52× · PMID 34800996 · DOI 10.1186/s12879-021-06829-7
6. COVID-19 convalescent plasma therapy: hit fast, hit hard!
   Focosi D, Franchini M. · · 2021 · cited 25× · PMID 33794556 · DOI 10.1111/vox.13091
7. Convalescent plasma for people with COVID-19: a living systematic review.
   Iannizzi C, Chai KL, Piechotta V, Valk SJ, et al · · 2023 · cited 24× · PMID 36734509 · DOI 10.1002/14651858.cd013600.pub5
8. CONVALESCENT plasma for COVID-19: A meta-analysis of clinical trials and real-world evidence.
   Kloypan C, Saesong M, Sangsuemoon J, Chantharit P, et al · · 2021 · cited 23× · PMID 34375445 · DOI 10.1111/eci.13663