Convalescent Plasma and Placebo for the Treatment of COVID-19 Severe Pneumonia

COVID-19 Clinical Trial

— PLASM-AR  

Official title:

Randomized, Double-blind, Placebo-controlled Clinical Trial of Convalescent Plasma for the Treatment of COVID-19 Pneumonia With Severity Criteria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04383535
• Other study ID #: 5565
• Status: Completed
• Phase: N/A
• Start date: May 15, 2020
• Est. completion date: September 27, 2020

Study information

• Verified date: September 2020
• Source: Hospital Italiano de Buenos Aires
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 333
• Est. completion date: September 27, 2020
• Est. primary completion date: September 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Pneumonia
• SARS Virus
• SARS-CoV-2

Intervention

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
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.

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autonoma de Buenos Aire	Ciudad Autonoma De Buenos Aires

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Italiano de Buenos Aires

Country where clinical trial is conducted

Argentina, 

References & Publications (8)

Angus DC. Optimizing the Trade-off Between Learning and Doing in a Pandemic. JAMA. 2020 May 19;323(19):1895-1896. doi: 10.1001/jama.2020.4984. — View Citation

Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, Chan P, Wong KC, Leung CB, Cheng G. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005 Jan;24(1):44-6. — View Citation

Kalil AC. Treating COVID-19-Off-Label Drug Use, Compassionate Use, and Randomized Clinical Trials During Pandemics. JAMA. 2020 May 19;323(19):1897-1898. doi: 10.1001/jama.2020.4742. — View Citation

Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med. 2006 Oct 17;145(8):599-609. Epub 2006 Aug 29. — View Citation

Maiztegui JI, Fernandez NJ, de Damilano AJ. Efficacy of immune plasma in treatment of Argentine haemorrhagic fever and association between treatment and a late neurological syndrome. Lancet. 1979 Dec 8;2(8154):1216-7. — View Citation

Roback JD, Guarner J. Convalescent Plasma to Treat COVID-19: Possibilities and Challenges. JAMA. 2020 Apr 28;323(16):1561-1562. doi: 10.1001/jama.2020.4940. — View Citation

Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Apr 28;323(16):1582-1589. doi: 10.1001/jama.2020.4783. — View Citation

Tanne JH. Covid-19: FDA approves use of convalescent plasma to treat critically ill patients. BMJ. 2020 Mar 26;368:m1256. doi: 10.1136/bmj.m1256. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical status during follow-up at 30th day	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.	30th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Secondary	Clinical status during follow-up at 7th day	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.	7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Secondary	Clinical status during follow-up at 14th day	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.	14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Secondary	Time until hospital discharge (days).	Hospital discharge or intrahospital death	Whenever the patient is discharge from the hospital or die without discharge, through study completion, an average of 14 days from admission
Secondary	Time until discharge from ICU (days)	ICU discharge or ICU death	Whenever the patient is discharge from ICU or die in ICU, through study completion, an average of 10 days from admission
Secondary	Time to death	Death and time to death	In a 30 days follow up period
Secondary	Time until complete functional recovery	Time until complete functional recovery (according to basal status).	Whenever the patient returns to basal functional status until 1 month from discharge
Secondary	Percentage of participants with adverse events / serious adverse events	Percentage of participants with adverse events / serious adverse events	In a 30 days follow up period
Secondary	Percentage of patients with negative SARS-CoV-3 PCR at Day 14th	Percentage of patients with negative SARS-CoV-3 PCR	14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Secondary	D Dimer plasma concentration at Day 14th	D Dimer plasma concentration	14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Secondary	Ferritin plasma concentration at Day 13th	Ferritin plasma concentration	13th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Secondary	Plasma concentration of neutralizing antibodies at Day 2nd	Plasma concentration of neutralizing antibodies	2nd Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Secondary	Plasma concentration of neutralizing antibodies at Day 7th	Plasma concentration of neutralizing antibodies	7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Secondary	Post-transfusion adverse reactions	Post-transfusion adverse reactions between study groups	In a 30 days follow up period