Clinical trial NCT04388410: Safety and Efficacy of Convalescent Plasma Transfusion for Patients With COVID-19
Official title: Phase 2b/3 Trial to Evaluate the Safety and Efficacy of Plasma Transfusion From Convalescent Patients With SARS-CoV-2 Infection on Severity and Mortality of COVID-19 in Hospitalized Patients.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: COVID-19
Keywords: SARS-CoV-2
convalescent plasma
randomized clinical trial
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
Collaborators: name: TecSalud Investigación Clínica
name: Instituto Nacional de Enfermedades Respiratorias
name: Instituto Nacional de Cardiologia Ignacio Chavez
name: Hospital General Dr. Manuel Gea González
name: Hospital Regional de Alta Especialidad del Bajio
name: Instituto Nacional de Cancerologia de Mexico
First posted: 2020-05-14
Enrollment: 410
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blinded, multicenter, placebo-controlled study
Primary purpose: TREATMENT

Brief summary: This is a multicenter double blinded study to evaluate the efficacy and safety of convalescent plasma from COVID-19 recovered individuals to treat hospitalized patients with severe COVID-19 disease. The study will enroll 410 subjects who will be randomized 1:1 to receive convalescent plasma or normal saline solution in a blinded manner. The primary endpoint will be improvement on the 8 point WHO scale over 28 days. Mortality at day 28 will be a secondary endpoint. An interim analysis will be done when 224 patients have completed their follow up to assess safety and to indicate continuation or stopping of the study, based on safety and efficacy observed.

Detailed description: A total of 410 patients with COVID 19 who fulfill inclusion criteria will be invited to receive:

Human convalescent plasma from recovered patients in two infusions of 200 ml separated with 24 to 72 hours or Normal saline solution in a similar plasma bag. Both products will be covered in an identical material to avoid identification of the infused product.

Primary endpoint:

Improvement on the 8 point WHO scale over 28 days.

Secondary endpoints.

Mortality at day 28

* Presence of antibodies against SARS-CoV-2 in serum on days 0, 3, 7, 14, 21 y 28 after plasma administration, as long as the patient remains in the hospital.
* Disease progression to a worse stage compared to the baseline on admission to the study according to SOFA scale.
* Disease progression to a worse stage defined as worsening in at least two categories in the OMS disease scale on different timelines in comparison to baseline on admission to the study
* Number of hours on mechanical ventilation in those who enter the study on mechanical ventilation.
* Number of days with fever defined as temperature \>38°C on at least one occasion during the day

Inclusion criteria:

1. Adults older than 18 years.
2. Confirmed SARS-CoV2 infection
3. Patient hospitalized for COVID 19
4. Severe disease or risk for severe disease
5. Informed consent from patient or responsible person.

Exclusion criteria

1. History of allergic reactions to blood products
2. SOFA scale \>12 points
3. Absolute contraindication for administration of plasma
4. Participation in other blinded clinical trial
5. Projected life expectancy less than 3 months
6. Any condition perceived by the investigator as not appropriate for participation of the patient in the trial.

Eligibility criteria: Inclusion Criteria:

1. Adults 18 years of age and older.
2. Confirmed SARS-CoV2 infection
3. Hospitalized for COVID 19
4. Severe disease or risk for severe disease
5. Informed consent from patient or responsible person.

Exclusion Criteria:

1. History of allergic reactions to blood products
2. SOFA scale \>12 points
3. Absolute contraindication for administration of plasma
4. Participation in other blinded clinical trial
5. Projected life expectancy less than 3 months
6. Any condition perceived by the investigator as not appropriate for participation of the patient in the trial.

Primary outcomes:
measure: Severity and death
timeFrame: 28 days
measure: Adverse events that require study treatment interruption
timeFrame: During the 28 day of follow up
Secondary outcomes:
measure: Time to clinical improvement
timeFrame: 28 days
measure: Severity and death
timeFrame: Days 1, 3, 5, 7, 12, 14, and 21.
measure: Antibodies against SARS-CoV-2
timeFrame: Days 0, 3, 7, 14, 21, 28
measure: Disease progression 1
timeFrame: 28 days
measure: Disease progression 2
timeFrame: Days 7,14, 21, 28
measure: Time on mechanical ventilation
timeFrame: 28 days
measure: Number of days with fever
timeFrame: 28 days
measure: Adverse events attributed to the study intervention
timeFrame: 28 days
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
state: Tlalpan
Study officials:
affiliation: Department of Infectious Diseases
name: Juan G Sierra-Madero, MD
role: PRINCIPAL_INVESTIGATOR
References: