Clinical trial NCT04393727: Transfusion of Convalescent Plasma for the Early Treatment of Patients With COVID-19
Official title: Transfusion of Convalescent Plasma for the Early Treatment of pneumonIa Due to SARSCoV2: a Multicenter Open Label Randomized Control Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID
SARS-CoV 2
Keywords: covid-19
SARS-CoV2
pneumonia
convalescent plasma
Lead sponsor: Azienda Ospedaliero, Universitaria Pisana
Sponsor class: OTHER
First posted: 2020-05-19
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: No specific therapeutic agents or vaccines for COVID-19 are available. Several therapies, are under investigation, but the antiviral efficacy of these drugs is not yet known. The use of convalescent plasma was recommended as an empirical treatment during outbreaks of Ebola virus in 2014, and a protocol for treatment of Middle East respiratory syndrome coronavirus with convalescent plasma was established in 2015. Accordingly, we hypothesized that use of convalescent plasma transfusion could be beneficial in patients infected with SARS-CoV-2.

This is a multicenter prospective randomized clinical trial to evaluate safety and efficacy of early use of convalescent plasma in patients with SARS-CoV2 pneumonia.

Primary endpoint will be the efficacy, evaluated as the need of invasive mechanical ventilation defined by PaO2/FiO2 ratio \<150.

Secondary endpoints will be: mortality rates, time to invasive mechanical ventilation, time to virological cure, length of hospital stay, toxicity.

Patients with SARS-CoV2 pneumonia not requiring mechanical ventilation (both non invasive and invasive) will be randomized 1:1 to receive or not convalescent plasma. Patients in the plasma group will receive 200 ml of convalescent plasma, continuing already administered standard therapy, while patients in the control group will continue to receive the standard therapy. A rescue therapy will be allowed in case of clinical worsening.

Patients will be followed-up until 30 days from randomization.

Detailed description: This is a multicenter prospective randomized open-label clinical trials. Patients with pneumonia due to SARS-CoV-2 will be included and randomized to receive or not convalescent plasma.

Convalescent plasma will be collected by cured patients with previous diagnosis of COVID-19. More specifically, inclusion and exclusion criteria for donors will be the following.

Inclusion criteria for donors:

* age \> 18 and \<60 years
* confirmed diagnosis of COVID-19: PCR on nasopharynx swab or positive IgG
* presence of 2 negative nasopharynx swabs for patients with previous positive swab and presence of 1 negative nasopharynx swab for patients with positive IgG

Exclusion criteria for donors:

* age \< 18 ys or \>60 ys
* other conditions that controindicate blood donation

Collected plasma will undergo all procedures for blood preparation. Plasma will be tested with enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody titers.

Patients eligible for the study will be selected among hospitalized patients with SARS-CoV2 pneumonia. More specifically, the following criteria will used for inclusion in the study.

Inclusion criteria for recipients:

* age \>18 ys
* confirmed diagnosis of SARS-CoV2 pneumonia
* PaO2/FiO2 200-350

Exclusion criteria for recipients:

* PaO2/FiO2 \<200
* need of non invasive or invasive mechanical ventilation

Patients will be randomized 1:1 to receive or not convalescent plasma. All patients will be followed-up for 30 days after randomization.

Primary endpoint will be the need of mechanical ventilation, defined as PaO2/FiO2 \<150.

Eligibility criteria: Inclusion Criteria:

* Any gender
* Age \> 18 years on day of signing informed consent
* Informed written consent for participation in the study
* Virological diagnosis of SARS-CoV-2 infection (real-time PCR)
* Hospitalized due to clinical instrumental diagnosis of pneumonia
* PaO2/FiO2 ratio 200-350

Exclusion Criteria:

* mechanical ventilation (both invasive and non-invasive)
* PaO2/FiO2\<200
* known hypersensitivity to immunoglobulin or blood components

Primary outcomes:
measure: Need of invasive mechanical ventilation
timeFrame: 30 days
Secondary outcomes:
measure: Mortality rates
timeFrame: 30 days
measure: Time to invasive mechanical ventilation
timeFrame: 30 days
measure: Time to virologic cure
timeFrame: 30 days
measure: Length of hospital stay
timeFrame: 30 days
measure: Adverse events
timeFrame: 30 days
Other outcomes:
Locations:
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
Study officials:
affiliation: Azienda Ospedaliero, Universitaria Pisana
name: Francesco Menichetti
role: PRINCIPAL_INVESTIGATOR
References:
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.