Effectiveness and Safety of Convalescent Plasma in Patients With High-risk COVID-19

Effectiveness and Safety of Convalescent Plasma in Patients With High-risk COVID-19: A Randomized, Controlled Study CRI-CP (Coronavirus Investigation - Convalescent Plasma)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the global population with significant morbidity and mortality. One of the main concerns is the management of the patients since there is no specific treatment for this condition. Therefore, in SARS-CoV-2 patients the compassionate use of off-label therapies has been initiated; such as the use of plasma from convalescent patients. This treatment has been used in other pandemics like SARS-CoV-1, H5N1, H1N1, Ebola, among others. This study is a phase II/III randomized clinical trial to assess the effectiveness and safety of convalescent plasma administration in patients with high-risk SARS-CoV-2.

Study Overview

• Status: Unknown
• Conditions: Covid-19; Sars-CoV2
• Intervention / Treatment: Other: Standard care; Biological: SARS-CoV-2 convalescent plasma treatment

Detailed Description

This is a Phase II/III randomized clinical trial to assess the effectiveness and safety of anti-SARS-CoV-2 convalescent plasma in i) hospitalized adult patients with high-risk of progression SARS-CoV-2 infection and ii) patients in Intensive Care Unit (ICU).

Compatible ABO plasma from convalescent patients will be administered at a dose of 400 ml divided into two doses intravenously. Outcomes will be measured as follows:

* Group of patients with critical illness:

Primary outcomes (Effectiveness and safety):

• Mortality
• Safety: Presence of adverse events

Secondary outcomes:

• Intensive care unit length of stay

• Evolution of clinical and paraclinical aspects.

  • Group of patients at high risk of progression:

Primary outcomes (Effectiveness and safety):

• Mortality
• Safety: Presence of adverse events
• Admission to ICU in 30 days
• Mechanical ventilation requirement

Secondary outcomes:

• Hospital/Intensive care unit length of stay
• Evolution of clinical and paraclinical aspects.

• Study Type: Interventional
• Enrollment (Anticipated): 236
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Colombia
  • Cundinamarca
    • Bogotá, Cundinamarca, Colombia, 110111
      • Fundacion Santa Fe de Bogota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All patients

• Patients diagnosed with COVID-19 infection by RT-PCR technique
• Patients ≥ 18 years of age
• Patients in standard care according to the national guide
• Onset of symptoms ≤ 14 days
• Signature of informed consent report

Patients at high risk of progression, defined by all of the following:

• Score greater than 9 on the CALL scale
• Pao2 / Fio2 ≤ 200 (parameters adjusted to the height of Bogotá, Colombia)
• X-ray or CT compatible with pneumonia
• Hospitalized patients

Critically ill patients, defined by any of the following:

• Mechanical ventilation requeriment
• Patients in Intensive Care Unit or Intermediate Care Unit
• Ventilatory failure, septic shock, dysfunction or multi-organ failure

Exclusion Criteria:

• Negative RT-PCR result from secretion 48 hours prior to study recruitment
• History of allergic reaction to blood or plasma in patients with a known history of IgA deficiency
• Patients participating in other clinical trial
• History of allergy to blood products
• History of confirmed infection and that required antibiotic or antifungal treatment 30 days prior to recruitment
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Standard care alone	Other: Standard care; Standard care according to guidelines and national regulations
EXPERIMENTAL: SARS-CoV-2 convalescent plasma treatment plus standard care	Other: Standard care; Standard care according to guidelines and national regulations; Biological: SARS-CoV-2 convalescent plasma treatment; Plasma transfusion of convalescent patients from COVID-19 with negative RT-PCR, and antibody titers of 1:160 or greater at a dose of 400ml distributed in two doses administered on the same day intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Death of the patient (yes/no)	Up to 30 days after the study enrollment
Adverse events	Presence of any of the following adverse events (yes/no): Nonhemolytic febrile reactions; Allergic reactions; Acute hemolytic reactions; Non-immune hemolysis; Acute transfusion-related lung damage; Transfusion-related circulatory overload; Metabolic reactions; Hypotensive reactions; Delayed hemolytic reactions; Post transfusion purple; Graft versus host disease; Bacterial contamination of blood components; Viral infections; Other infections (syphilis, prions, malaria, Chagas, yellow fever, dengue)	Up to 30 days after the study enrollment
ICU admission	Admitted to intensive care units (ICUs) (yes/no)	Up to 30 days after the study enrollment
Mechanical ventilation	Mechanical ventilation requirement (yes/no)	Up to 30 days after the study enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU length	Intensive care unit length of stay	Up to 30 days after the study enrollment
Reduction of D Dimer	D dimer reduction below 1mcg / ml	Assessment at day 30 after study enrollment
LDH reduction	Reduction of LDH below 350 IU / L	Assessment at day 30 after study enrollment
Reduction of Troponin level	Reduction of troponin level to than 8 pg / mL	Assessment at day 30 after study enrollment
Decrease in ferritin level	Decrease in ferritin level below 1025 mcg / L	Assessment at day 30 after study enrollment
Decrease in procalcitonin level	Decrease in procalcitonin level below 0.1ng / ml	Assessment at day 30 after study enrollment
Decrease in CRP	Decrease in CRP level bellow <8 mg / L	Assessment at day 30 after study enrollment
Increase in lymphocyte count	Increase in lymphocyte count greater than 0.6 x 10-9 / L	Assessment at day 30 after study enrollment
Increase in PaO2 / Fio2	Increase in PaO2 / Fio2 greater than 200	Assessment at day 30 after study enrollment
Decrease in Sequential Organ failure assessment (SOFA ) score	Scale of 24 points, greater number indicates worst outcome	Assessment at day 30 after study enrollment
Extracorporeal membrane oxygenation (ECMO)	Extracorporeal membrane oxygenation requirement (ECMO)	Assessment at day 30 after study enrollment
Lung infiltration	Decrease in the percentage of lung infiltration	Assessment at day 30 after study enrollment

Collaborators and Investigators

• Sponsor: Fundación Santa Fe de Bogota

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 1, 2020
• Primary Completion (ANTICIPATED): February 1, 2021
• Study Completion (ANTICIPATED): February 1, 2021

Study Registration Dates

• First Submitted: May 29, 2020
• First Submitted That Met QC Criteria: June 8, 2020
• First Posted (ACTUAL): June 11, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 8, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Safety; Mortality; COVID-19 serotherapy
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: PLASMA COVID-19

Drug and device information, study documents

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