Convalescent Plasma and Placebo for the Treatment of COVID-19 Severe Pneumonia (PLASM-AR)
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| ClinicalTrials.gov Identifier: NCT04383535 |
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Recruitment Status :
Completed
First Posted : May 12, 2020
Last Update Posted : September 30, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| SARS Virus SARS-CoV-2 COVID-19 | Other: Convalescent SARS COVID-19 plasma Other: Placebo | Not Applicable |
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
| 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 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Convalescent SARS COVID-19 plasma
Convalescent SARS COVID-19 plasma from a pool of 10 donor plasma, in addition to standard care.
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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. |
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Placebo Comparator: Placebo
Single infusion of saline solution, in addition to standard care.
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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. |
- 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.
- 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.
- 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.
- 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
- 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
- Time to death [ Time Frame: In a 30 days follow up period ]Death and time to death
- 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).
- 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
- 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
- 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
- Ferritin plasma concentration at Day 13th [ Time Frame: 13th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) ]Ferritin plasma concentration
- 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
- 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
- Post-transfusion adverse reactions [ Time Frame: In a 30 days follow up period ]Post-transfusion adverse reactions between study groups
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
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
| Argentina | |
| Hospital Italiano de Buenos Aires | |
| Ciudad Autonoma de Buenos Aire, Ciudad Autonoma De Buenos Aires, Argentina, 1181 | |
| 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 |
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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SARS Virus SARS-CoV-2 COVID-19 Blood Plasma |
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Pneumonia Lung Diseases Respiratory Tract Diseases Respiratory Tract Infections |