Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Convalescent Plasma and Placebo for the Treatment of COVID-19 Severe Pneumonia (PLASM-AR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04383535
Recruitment Status : Completed
First Posted : May 12, 2020
Last Update Posted : September 30, 2020
Sponsor:
Information provided by (Responsible Party):
Hospital Italiano de Buenos Aires

Brief Summary:
A multicenter randomized, double-blind, placebo-controlled clinical trial of Convalescent SARS COVID-19 plasma versus Placebo to evaluate the effect between arms on an ordinal score of six mutually exclusive categories of clinical status at day 30 after study initiation.

Condition or disease Intervention/treatment Phase
SARS Virus SARS-CoV-2 COVID-19 Other: Convalescent SARS COVID-19 plasma Other: Placebo Not Applicable

Detailed Description:

Introduction

The use of convalescent plasma in the treatment of infectious diseases has been empirically performed for more than a century. It is based upon the assumption that providing exogenous neutralizing antibodies may provide protection while affected patients mount their own immune response. This therapeutic approach appears of particular interest in the context of the current pandemic, in which there is no specific vaccine available nor adequately proven effective pharmacological treatments.

Study purpose, hypothesis and general design

Purpose of the study: evaluate the effectiveness and safety of convalescent plasma in the treatment of SARS-CoV-2 pneumonia (Covid-19) Hypothesis: Convalescent plasma significantly improves the clinical outcome in patients with Covid-19 pneumonia and severity criteria.

Multicenter randomized, double-blind, placebo.controlled clinical trial. Placebo will be a saline solution.

3. Methodological sustain for including a control arm with placebo Quality evidence about the effectiveness of convalescent plasma in the treatment of Covid-19 pneumonia is not yet available. Although case series and anecdotal reports appear encouraging, the implementation of its use in routine clinical practice requires the validation through controlled clinical trials. In addition the collection, administration and control of plasma is technically demanding and needs a clear support before broadly recommending it. Different scientific institutions and international organisms had clearly suggested to prioritize the application of novel therapeutic techniques with yet unproven efficacy within the context of clinical studies over its empirical use.

On the other hand, for the present study, intervention strategy is proposed in "add-on" modality over the antiviral treatment that each participant may be already receiving, since they represent completely different therapeutic approaches. As such, participation in the present study will not condition the possibility of the participants to receive other treatments, either in intervention or control arms.

4. Study objectives Primary objective Analyze the difference between arms on an ordinal score of six mutually exclusive categories at day 30 after study initiation. This score includes the following categories

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 333 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multicenter randomized (2:1, 222 plasma 111 placebo), double-blind, placebo-controlled clinical trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The pharmacist will be unblinded. The study intervention will be covered with an opaque development in order to ensure blinding of the intervention arm.
Primary Purpose: Treatment
Official Title: Randomized, Double-blind, Placebo-controlled Clinical Trial of Convalescent Plasma for the Treatment of COVID-19 Pneumonia With Severity Criteria
Actual Study Start Date : May 15, 2020
Actual Primary Completion Date : September 27, 2020
Actual Study Completion Date : September 27, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Experimental: Convalescent SARS COVID-19 plasma
Convalescent SARS COVID-19 plasma from a pool of 10 donor plasma, in addition to standard care.
Other: Convalescent SARS COVID-19 plasma
Convalescent SARS COVID-19 plasma from a pool of 10 donor plasma. The calculation of the volume to be transfused will be from 10 to 15 ml / kg adjusting the volume to the body weight of each patient, at a suggested infusion rate of 5 to 10 ml / kg / h with an intravenous infusion pump. The infusion rate will be adjusted according to the clinical stability of the patient according to the treating physician.

Placebo Comparator: Placebo
Single infusion of saline solution, in addition to standard care.
Other: Placebo
Single infusion of saline solution, in addition to standard care. The calculation of the volume to be transfused will be from 10 to 15 ml / kg adjusting the volume to the body weight of each patient, at a suggested infusion rate of 5 to 10 ml / kg / h with an intravenous infusion pump. The infusion rate will be adjusted according to the clinical stability of the patient according to the treating physician.




Primary Outcome Measures :
  1. Clinical status during follow-up at 30th day [ Time Frame: 30th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) ]
    Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.


Secondary Outcome Measures :
  1. Clinical status during follow-up at 7th day [ Time Frame: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) ]
    Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

  2. Clinical status during follow-up at 14th day [ Time Frame: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) ]
    Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

  3. Time until hospital discharge (days). [ Time Frame: Whenever the patient is discharge from the hospital or die without discharge, through study completion, an average of 14 days from admission ]
    Hospital discharge or intrahospital death

  4. Time until discharge from ICU (days) [ Time Frame: Whenever the patient is discharge from ICU or die in ICU, through study completion, an average of 10 days from admission ]
    ICU discharge or ICU death

  5. Time to death [ Time Frame: In a 30 days follow up period ]
    Death and time to death

  6. Time until complete functional recovery [ Time Frame: Whenever the patient returns to basal functional status until 1 month from discharge ]
    Time until complete functional recovery (according to basal status).

  7. Percentage of participants with adverse events / serious adverse events [ Time Frame: In a 30 days follow up period ]
    Percentage of participants with adverse events / serious adverse events

  8. Percentage of patients with negative SARS-CoV-3 PCR at Day 14th [ Time Frame: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) ]
    Percentage of patients with negative SARS-CoV-3 PCR

  9. D Dimer plasma concentration at Day 14th [ Time Frame: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) ]
    D Dimer plasma concentration

  10. Ferritin plasma concentration at Day 13th [ Time Frame: 13th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) ]
    Ferritin plasma concentration

  11. Plasma concentration of neutralizing antibodies at Day 2nd [ Time Frame: 2nd Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) ]
    Plasma concentration of neutralizing antibodies

  12. Plasma concentration of neutralizing antibodies at Day 7th [ Time Frame: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) ]
    Plasma concentration of neutralizing antibodies

  13. Post-transfusion adverse reactions [ Time Frame: In a 30 days follow up period ]
    Post-transfusion adverse reactions between study groups



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of Covid-19 through qualitative polymerase-reverse transcriptase (qRT-PCR -GeneDX Co, Ltd o similar).
  • Imagining-diagnosed pneumonia (Rx or CT scan).
  • MSOFA score (Modified SOFA) of 2 or more (modified organic failure assessment)
  • Informed consent.

Exclusion Criteria:

  • Pregnant women
  • Women at reproductive age not willing to avoid unprotected sexual intercourse up to Day 30 after study initiation.
  • Women in the breastfeeding period
  • Patients receiving experimental treatments under development within 30 days prior to study initiation.
  • Patients with a previous history of allergic reactions to blood or blood-components transfusion.
  • Diagnosis or clinical suspicion of an alternative microbiological cause for pneumonia besides COVID-19
  • Use of systemic corticosteroids within 15 days prior to entering the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04383535


Locations
Layout table for location information
Argentina
Hospital Italiano de Buenos Aires
Ciudad Autonoma de Buenos Aire, Ciudad Autonoma De Buenos Aires, Argentina, 1181
Sponsors and Collaborators
Hospital Italiano de Buenos Aires
Investigators
Layout table for investigator information
Principal Investigator: Nora A Fuentes, MD Hospital Privado de la Comunidad de Mar del Plata
Principal Investigator: Florencia Otermin, MD Hospital Italiano de la Plata
Principal Investigator: Esteban Nannini, MD Sanatorio Britanico Rosario, pcia Santa Fe
Principal Investigator: Karina Rainiero, MD Suiza Argentina
Principal Investigator: Erica Miyazaki, MD Clinica Zabala
Principal Investigator: Gabriela Vidiella, MD Sanatorio Agote
Principal Investigator: Wanda Cornistein, MD Austral University, Argentina
Principal Investigator: Leandro Burgos, MD Hospital Italiano de Buenos Aires
Publications of Results:
Other Publications:
Layout table for additonal information
Responsible Party: Hospital Italiano de Buenos Aires
ClinicalTrials.gov Identifier: NCT04383535    
Other Study ID Numbers: 5565
First Posted: May 12, 2020    Key Record Dates
Last Update Posted: September 30, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospital Italiano de Buenos Aires:
SARS Virus
SARS-CoV-2
COVID-19
Blood Plasma
Additional relevant MeSH terms:
Layout table for MeSH terms
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections