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

COVID Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04479163
• Other study ID #: FundacionINFANT-Plasma
• Status: Completed
• Phase: N/A
• Start date: June 4, 2020
• Est. completion date: October 25, 2020

Study information

• Verified date: December 2020
• Source: Fundacion Infant
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 165
• Est. completion date: October 25, 2020
• Est. primary completion date: October 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• Age = 75 or age 65-74 with at least 1 of the following comorbidities: arterial hypertension, diabetes, obesity, chronic obstructive pulmonary disease, heart disease, chronic kidney disease

• Last 48 hours: (A)Axillary temperature = 37.5oC or febrile equivalent, combined with (a) dry cough and/or (b) breathing difficulty and/or (c) odinophagia and/or (d) anosmia/dysgeusia and/or (e) any of the following symptoms: fatigue, anorexia, myalgias or rhinorrhea.

• Confirmed diagnosis SARS-Cov2 by RT-PCR

• Give Informed consent

Exclusion Criteria:

• Severe respiratory disease

• Cardiac insufficiency,

• Chronic renal failure,

• Primary hypogammaglobulinemias,

• Myelodysplastic syndromes,

• Chronic linfoproliferative syndromes,

• Monoclonal gammapathies,

• Known hypersensitibility,

• Active cancer,

• HIV, HBV or HCV infection,

• Chronic administration of immunosuppressants,

• Body transplant history,

• Chronic liver disease, Chronic lung disease with oxygen requirement.

Related Conditions & MeSH terms

• COVID

Intervention

Biological:
• Convalescent Plasma
250 ml Convalescent plasma with an IgG titer against SARS CoV2

Other:
• Placebo
Normal Saline 0.9%

Locations

Country	Name	City	State
Argentina	Clinica Olivos	Buenos Aires
Argentina	Hospital Central de San Isidro	Buenos Aires
Argentina	Hospital General de Agudos "Dr. Carlos Bocalandro"	Buenos Aires
Argentina	CEMIC	Caba	Buenos Aires
Argentina	Centro de Investigacion Clinica OSECAC	Caba	Buenos Aires
Argentina	Centro Gallego de Buenos Aires	Caba	Buenos Aires
Argentina	Hospital Militar Central	Caba	Buenos Aires
Argentina	Sanatorio Anchorena	Caba	Buenos Aires
Argentina	Sanatorio de Los Arcos	Caba	Buenos Aires
Argentina	Hospital "Simplemente Evita"	González Catán	Buenos Aires
Argentina	Hospital Especializado de Agudos y Crónicos "San Juan de Dios"	La Plata	Buenos Aires

Sponsors (1)

Lead Sponsor	Collaborator
Fundacion Infant

Country where clinical trial is conducted

Argentina, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Development of severe respiratory disease defined as a respiratory rate (RR)>30 and/or an O2 sat<93%		From 12 hours post infusion to day 15 post infusion
Secondary	Life threatening respiratory disease		From 12 hours post infusion to day 25 post infusion
Secondary	Critical systemic illness, defined as respiratory failure		From 12 hours post infusion to day 25 post infusion
Secondary	Death		From 12 hours post infusion to day 25 post infusion
Secondary	Combination of secondary outcomes #2 (Life threatening respiratory disease) and/or #3 (Critical systemic illness, defined as respiratory failure) and//or #4 (death)		From 12 hours post infusion to day 25 post infusion
Secondary	Duration of oxygen support requirement in patients with covid-19 due to saturation in ambient air <93%.		From 12 hours post infusion to day 25 post infusion