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Safety and Efficacy of Convalescent Plasma Transfusion for Patients With COVID-19

Phase 2
Conditions
COVID-19
Interventions
Biological: convalescent plasma
Registration Number
NCT04388410
Lead Sponsor
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
410
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Normal salineconvalescent plasmaNormal saline solution in 200 ml plasma bags enclosed with with a similar material as the plasma
convalescent plasmaconvalescent plasmaConvalescent plasma obtained from volunteers who have recovered from COVID 19. Enclosed with a similar material as the control
Primary Outcome Measures
NameTimeMethod
Severity and death28 days

Ordinal 8-point severity outcome scale: 1 Death, 2 Hospitalized, intubated and receiving mechanical ventilation and additional organ support (eg. renal replacement therapy, vasopressors, extracorporeal membrane oxygenation), 3 Hospitalized, intubated and receiving mechanical ventilation but no additional organ support, 4 Hospitalized receiving non-invasive ventilation of high-flow oxygen, 5 Hospitalized, receiving supplementary oxygen by mask or nasal prongs, 6 Hospitalized, no oxygen therapy needed, 7 Not-hospitalized (ambulatory) with limited activity, 8 Not-hospitalized (ambulatory) with no limitation of activities.

Adverse events that require study treatment interruptionDuring the 28 day of follow up

Any unfavorable and unintended symptom or sign (including an abnormal laboratory finding) temporally associated with the study intervention and considered related to the intervention that require interruption of study treatment. Including but not limited to: Severe allergic reactions (rash and fever), transfusion-associated lung injury (TRALI), transfusion-associated circulatory overload (TACO), and other severe unexpected events

Secondary Outcome Measures
NameTimeMethod
Disease progression 2Days 7,14, 21, 28

Changes in at least two categories in the 8-point ordinal severity scale in comparison to baseline on admission to the study

Disease progression 128 days

Changes in SOFA scale during hospitalization compared to the baseline

Number of days with fever28 days

Temperature \>=38°C on at least one measurement during the day

Time to clinical improvement28 days

Time (in days) to improvement in at least two categories in the 8-point ordinal severity scale in comparison to baseline on admission to the study.

Adverse events attributed to the study intervention28 days

Any unfavorable and unintended symptom or sign (including an abnormal laboratory finding) temporally associated with the study intervention and considered related to the intervention.

Time on mechanical ventilation28 days

Time (in hours) spent receiving invasive mechanical ventilation in those who enter the study on mechanical ventilation.

Severity and deathDays 1, 3, 5, 7, 12, 14, and 21.

Ordinal 8-point severity outcome scale: 1 Death, 2 Hospitalized, intubated and receiving mechanical ventilation and additional organ support (eg. renal replacement therapy, vasopressors, extracorporeal membrane oxygenation), 3 Hospitalized, intubated and receiving mechanical ventilation but no additional organ support, 4 Hospitalized receiving non-invasive ventilation of high-flow oxygen, 5 Hospitalized, receiving supplementary oxygen by mask or nasal prongs, 6 Hospitalized, no oxygen therapy needed, 7 Not-hospitalized (ambulatory) with limited activity, 8 Not-hospitalized (ambulatory) with no limitation of activities.

Antibodies against SARS-CoV-2Days 0, 3, 7, 14, 21, 28

Antibody titers on serum/plasma as long as the patient remains in the hospital.

Trial Locations

Locations (1)

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

🇲🇽

Mexico City, Tlalpan, Mexico

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