Convalescent Plasma for Patients With COVID-19: A Randomized, Single Blinded, Parallel, Controlled Clinical Study (CP-COVID-19)

Convalescent plasma (CP) has been used in recent years as an empirical treatment strategy when there is no vaccine or treatment available for infectious diseases. In the latest viral epidemics, such as the Ebola outbreak in West Africa in 2014, the World Health Organization issued a document outlining a protocol for the use of whole blood or plasma collected from patients who have recovered from the Ebola virus disease by transfusion to empirically treat local infectious outbreaks

Study Overview

• Status: Completed
• Conditions: Coronavirus Infection; Coronavirus
• Intervention / Treatment: Drug: Plasma; Drug: Standard Therapy

Detailed Description

The process is based on obtaining plasma from patients recovered from COVID-19 in Colombia, and through a donation of plasma from the recovered, the subsequent transfusion of this to patients infected with coronavirus disease (COVID-19). Our group has reviewed the scientific evidence regarding the application of convalescent plasma for emergency viral outbreaks and has recommended the following protocol

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Colombia
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 11100
      • Universidad del Rosario

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:Fulfilling all the following criteria

1. Olerder than 18.
2. Hospitalized participants with diagnosis of COVID 19 by Real Time - Polymerase Chain Reaction.
3. Severe cases according to the official guideline "Pneumonia Diagnosis and Treatment Scheme for Novel Coronavirus Infection (Trial Version 7)".
4. Sequential Organ Failure Assessment score (SOFA) < 6.
5. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Female subjects who are pregnant or breastfeeding.
2. Patients with prior allergic reactions to transfusions.
3. Critical ill patients in intensive care units with requierment of Invasive Mechanical Venitlation.
4. Patients with surgical procedures in the last 30 days.
5. Patients with active treatment for cancer (Radiotherapy or Chemotherapy).
6. HIV diagnosed patients with viral failure (detectable viral load> 1000 copies / ml persistent, two consecutive viral load measurements within a 3 month interval, with medication adherence between measurements after at least 6 months of starting a new regimen antiretrovirals).
7. Demonstrated coinfection that explains the patient's symptoms
8. End-stage chronic kidney disease (Glomerular Filtration Rate <15 ml / min / 1.73 m2).
9. Child Pugh C stage liver cirrhosis.
10. High cardiac output diseases.
11. Autoimmune diseases or Immunoglobulin A nephropathy.
12. Patients have any condition that in the judgement of the Investigators would make the subject inappropriate for entry into this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group; Participants included in the experimental group will receive 500 milliliters of convalescent plasma, distributed in two 250 milliliters transfusions on the first and second day after starting the protocol. Simultaneously, they will receive the standard therapy defined by institutional protocol.	Drug: Plasma; Day 1: CP-COVID19, 250 milliliters. Day 2: CP-COVID19, 250 milliliters.; Other Names: Convalescent Plasma COVID-19; Drug: Standard Therapy; Standard therapy defined by institutional protocol.
Active Comparator: Control Group; Participants included in the control group will receive standard therapy defined by institutional protocol.	Drug: Standard Therapy; Standard therapy defined by institutional protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Viral Load	Copies of COVID-19 per ml	Days 0, 4, 7, 14 and 28
Change in Immunoglobulin G COVID-19 Titers	Immunoglobulin G COVID-19 antibodies	Days 0, 4, 7, 14 and 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intensive Care Unit Admission	Proportion of patients with Intensive Care Unit Admission requirement (days 7, 14 and 28)	Days 7, 14 and 28
Length of Intensive Care Unit stay	Days of Intensive Care Unit management (days 7, 14 and 28)	Days 7, 14 and 28
Length of hospital stay (days)	Days of Hospitalization (days 7, 14 and 28)	Days 7, 14 and 28
Requirement of mechanical ventilation	Proportion of patients with mechanical ventilation (days 7, 14 and 28)	Days 7, 14 and 28
Duration (days) of mechanical ventilation	Days with mechanical ventilation (days 7, 14 and 28)	Days 7, 14 and 28
Clinical status assessed according to the World Health Organization guideline	1. Hospital discharge; 2. Hospitalization, not requiring supplemental oxygen; 3. Hospitalization, requiring supplemental oxygen (but not Noninvasive Ventilation/ HFNC); 4. Intensive care unit/hospitalization, requiring Noninvasive Ventilation/ HFNC therapy; 5. Intensive care unit, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; 6. Death. (days 7, 14 and 28)	Days 7, 14 and 28
Mortality	Proportion of death patients at days 7, 14 and 28	Days 7, 14 and 28

Collaborators and Investigators

• Sponsor: Universidad del Rosario
• Collaborators: CES University; Fundación Universitaria de Ciencias de la Salud; Instituto Distrital de Ciencia Biotecnología e Innovacion en Salud
• Investigators: Study Director: Juan M Anaya Cabrera, MD, PhD, Universidad del Rosario

Publications and helpful links

General Publications

• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum In: Lancet. 2020 Jan 30;:
• Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, Ng OT, Marimuthu K, Ang LW, Mak TM, Lau SK, Anderson DE, Chan KS, Tan TY, Ng TY, Cui L, Said Z, Kurupatham L, Chen MI, Chan M, Vasoo S, Wang LF, Tan BH, Lin RTP, Lee VJM, Leo YS, Lye DC; Singapore 2019 Novel Coronavirus Outbreak Research Team. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. 2020 Apr 21;323(15):1488-1494. doi: 10.1001/jama.2020.3204. Erratum In: JAMA. 2020 Apr 21;323(15):1510.
• Wang Y, Wang Y, Chen Y, Qin Q. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures. J Med Virol. 2020 Jun;92(6):568-576. doi: 10.1002/jmv.25748. Epub 2020 Mar 29.
• Infectious, D. & Outbreaks, D. Maintaining a safe and adequate blood supply during the pandemic outbreak of coronavirus disease ( COVID-19 ). OMS 1-5 (2020)
• Rojas M, Rodriguez Y, Hernandez JC, Diaz-Coronado JC, Vergara JAD, Velez VP, Mancilla JP, Araujo I, Yepes JT, Ricaurte OB, Pardo-Oviedo JM, Monsalve DM, Acosta-Ampudia Y, Ramirez-Santana C, Garcia PG, Landinez LA, Correales LD, Grass JS, Perez CR, Lopez GS, Mateus N, Mancera L, Devia RR, Orjuela JE, Parra-Moreno CR, Buitrago AA, Ordonez IE, Osorio CF, Ballesteros N, Patino LH, Castaneda S, Munoz M, Ramirez JD, Bastard P, Gervais A, Bizien L, Casanova JL, Camacho B, Gallo JE, Gomez O, Rojas-Villarraga A, Perez CE, Manrique R, Mantilla RD, Anaya JM. Safety and efficacy of convalescent plasma for severe COVID-19: a randomized, single blinded, parallel, controlled clinical study. BMC Infect Dis. 2022 Jun 27;22(1):575. doi: 10.1186/s12879-022-07560-7.

Helpful Links

• FDA recommendations for convalescent plasma clinical research

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2020
• Primary Completion (Actual): October 31, 2020
• Study Completion (Actual): November 15, 2020

Study Registration Dates

• First Submitted: March 31, 2020
• First Submitted That Met QC Criteria: April 1, 2020
• First Posted (Actual): April 3, 2020

Study Record Updates

• Last Update Posted (Actual): November 27, 2020
• Last Update Submitted That Met QC Criteria: November 25, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: COVID-19; Coronavirus Disease 2019
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections
• Other Study ID Numbers: ABN011-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No