TranSfUsion of coNvalescent plAsma for the Early Treatment of pneuMonIa in COVID-19 Patients

TranSfUsion of coNvalescent plAsma for the Early Treatment of pneuMonIa Due to SARS-CoV2 (TSUNAMI Study): a Multicenter Open Label Randomized Control Trial

This is a multicenter open-label randomized study for the early treatment of pneumonia due to SARS-COV2 with transfusion of convalescent plasma.

Patients with pneumonia due to SARS-CoV-2 will be randomized to receive or not convalescent plasma collected by recovered patients with previous diagnosis of COVID19

Study Overview

• Status: Completed
• Conditions: Coronavirus Infection; Pneumonia, Viral; Covid19
• Intervention / Treatment: Biological: Convalescent plasma

Detailed Description

This is a multicenter open-label randomized study for the early treatment of pneumonia due to SARS-COV2 with transfusion of convalescent plasma.

Patients with SARS-CoV2 pneumonia not requiring mechanical ventilation (both non invasive and invasive) will be randomized to receive or not convalescent plasma.

Patients in the plasma group will receive 200-300 ml of plasma collected by recovered patients with previous diagnosis of COVID19, plus standard therapy; Patients in the control group will receive the standard therapy. A rescue therapy will be allowed in case of clinical worsening.

Patients will be followed until day n30 from randomization.

• Study Type: Interventional
• Enrollment (Actual): 474
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Ancona, Italy
    • SOD Clinica Malattie Infettive Tropicali, Parassitologia, Epatiti Croniche - AOU Ospedali Riuniti di Ancona
  • Arezzo, Italy
    • Ospedale di Arezzo
  • Bari, Italy
    • Clinica Malattie Infettive, Università degli Studi di Bari
  • Bergamo, Italy
    • Ospedale Papa Giovanni XXIII-Dip. emergenza, Urgenza e area critica
  • Bologna, Italy
    • UOC Malattie Infettive - AOU Bologna
  • Catania, Italy
    • UO PID Tossicologia Applicata - Dip. Scienze Biomediche e Biotecnologiche - Università di Catania - AOU Policlinico Vittorio Emanuele
  • Città Di Castello, Italy
    • Ospedale Città di Castello
  • Empoli, Italy
    • Ospedale di Empoli
  • Fermo, Italy
    • UOC Malattie Infettive - ASUR Marche Area Vasta 4
  • Ferrara, Italy
    • UOC Malattie Infettive - AOU Ferrara
  • Firenze, Italy
    • OSpedale Santa Maria Annunziata
  • Firenze, Italy
    • SOD Malattie Infettive e Tropicali - AOU Careggi
  • Foggia, Italy
    • Dip.Medicina Clinica e Sperimentale - Policlinico "Riuniti" di Foggia
  • Foligno, Italy
    • Nuovo Ospedale S. Giovanni Battista Usl Umbria2
  • Frosinone, Italy
    • U.O.C. Malattie Infettive ASL Frosinone
  • Genova, Italy
    • U.O. Malattie Infettive IRCCS-Ospedale Policlinico San Martino
  • Grosseto, Italy
    • Ospedale di Grosseto
  • La Spezia, Italy
    • ASL 5 Spezzina - SC Malattie Infettive
  • Lecco, Italy
    • ASST Lecco - Malattie Infettive
  • Livorno, Italy
    • Ospedale di Livorno
  • Lucca, Italy
    • Ospedale di Lucca
  • Mantova, Italy
    • S.C. Pneumologia e Utir ASST Mantova - Ospedale Carlo Poma
  • Mestre, Italy
    • Ospedale Dell'Angelo - UOC Malattie Infettive
  • Milano, Italy
    • Ospedale Luigi Sacco
  • Milano, Italy
    • ASST Santi Paolo e Carlo
  • Milano, Italy
    • SC Malattie Infettive ASST Grande Ospedale Metropolitano Niguarda
  • Monza, Italy
    • Ospedale San Gerardo
  • Napoli, Italy
    • Malattie Infettive - AOU Federico II di Napoli
  • Napoli, Italy
    • UOC Malattie Infettive ad indirizzo Respiratorio - PO Cotugno - AORN "Dei Colli"
  • Palermo, Italy
    • UOC Malattie Infettive e Tropicali - AOU Policlinico
  • Pavia, Italy
    • Dip. Medicina Diagnost. e Servizi Fondazione IRCCS Policlinico San Matteo
  • Perugia, Italy
    • Azienda Ospedaliero-Universitaria di Perugia
  • Pesaro, Italy
    • UOC Malattie Infettive - Azienda Ospedali Riuniti Marche Nord
  • Pisa, Italy
    • AOU Pisana
  • Pistoia, Italy
    • Ospedale Pistoia
  • Prato, Italy
    • Ospedale Prato
  • Ravenna, Italy
    • Malattie Infettive Ravenna
  • Reggio Emilia, Italy
    • UOC Malattie Infettive - AUSL Reggio Emilia
  • Rimini, Italy
    • Malattie Infettive - Rimini Forlì Cesena
  • Roma, Italy
    • Campus Bio Medico - UO Anestesia e Rianimazione
  • Sanremo, Italy
    • ASL 1 Imperiese - SC Malattie Infettive
  • Savona, Italy
    • ASL 2 Savonese - SC Malattie Infettive
  • Siena, Italy
    • Ospedale di Siena
  • Sondrio, Italy
    • Ospedale di Sondrio - dipartimento di Medicina
  • Terni, Italy
    • AOU di Terni
  • Treviso, Italy
    • Ospedale Ca Foncello - UOC Malattie Infettive
  • Verona, Italy
    • A.O. Integrata Università di Verona
  • Viareggio, Italy
    • Ospedale Viareggio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years old

• adult patients with positive RT-PCR test for SARS-CoV2 (nasal swabs or lower respiratory tract sample), diagnosed with pneumonia (<= 10 days) according to the following definitions:

  • Suggestive radiological imaging (CT, RX, ultrasound);
  • Respiratory failure not fully explained by heart failure or fluid overload;
  • PaO2/FiO2 200-350 mmHg;
  • Signed informed consent

Exclusion Criteria:

• need of non invasive or invasive mechanical ventilation at the time of randomization;
• PaO2/FiO2 <200;
• patients with hypersensitivity or allergic reaction to blood products or immunoglobulins;
• patients who expressly refuse to adhere the clinical study;
• use of IL-6 Receptor inhibitors, IL-1 inhibitors, JAK inhibitors, TNF inhibitors;
• patients participating to other clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard Therapy+Convalescent Plasma; Patients will receive standard therapy + 200-300 ml of convalescent plasma for a maximum of 3 times in 5 days, according to clinical conditions.	Biological: Convalescent plasma; Convalescent plasma will be collected by healthy donors, recovered by COVID19 and, after standard preparation and dosage of neutralizing antibodies, it will be administered to patients with SARS-CoV2 pneumonia
No Intervention: Standard Therapy; Patients will receive standard therapy for the treatment of SARS-CoV2 infection, according to AIFA indications

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients who meet invasive mechanical ventilation or death	Number of patients who meet invasive mechanical ventilation defined as PaO2/FiO2 <150 or death	at 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rates	Mortality rates at 30 days	30 days
Time to invasive mechanical ventilation or death	Days from randomization to invasive mechanical ventilation or death	30 days
Time to virologic recover	Days from randomization to virologic recover (defined as 2 consecutive negative nasopharynx tests)	30 days
Hospitalization time		30 days
Adverse events	occurrence of Adverse events	30 days

Other Outcome Measures

Outcome Measure	Time Frame
Evaluation of CD4/CD8 ratio	14 days

Collaborators and Investigators

• Sponsor: Istituto Superiore di Sanità
• Collaborators: Gruppo Italiano Malattie EMatologiche dell'Adulto; Agenzia Italiana del Farmaco

Publications and helpful links

General Publications

• Menichetti F, Popoli P, Puopolo M, Spila Alegiani S, Tiseo G, Bartoloni A, De Socio GV, Luchi S, Blanc P, Puoti M, Toschi E, Massari M, Palmisano L, Marano G, Chiamenti M, Martinelli L, Franchi S, Pallotto C, Suardi LR, Luciani Pasqua B, Merli M, Fabiani P, Bertolucci L, Borchi B, Modica S, Moneta S, Marchetti G, d'Arminio Monforte A, Stoppini L, Ferracchiato N, Piconi S, Fabbri C, Beccastrini E, Saccardi R, Giacometti A, Esperti S, Pierotti P, Bernini L, Bianco C, Benedetti S, Lanzi A, Bonfanti P, Massari M, Sani S, Saracino A, Castagna A, Trabace L, Lanza M, Focosi D, Mazzoni A, Pistello M, Falcone M; TSUNAMI Study group. Effect of High-Titer Convalescent Plasma on Progression to Severe Respiratory Failure or Death in Hospitalized Patients With COVID-19 Pneumonia: A Randomized Clinical Trial. JAMA Netw Open. 2021 Nov 1;4(11):e2136246. doi: 10.1001/jamanetworkopen.2021.36246. Erratum In: JAMA Netw Open. 2021 Dec 1;4(12):e2144236. JAMA Netw Open. 2022 Jan 4;5(1):e2146944.

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2020
• Primary Completion (Actual): January 14, 2021
• Study Completion (Actual): May 31, 2021

Study Registration Dates

• First Submitted: January 14, 2021
• First Submitted That Met QC Criteria: January 19, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): August 26, 2021
• Last Update Submitted That Met QC Criteria: August 25, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: plasma
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; COVID-19; Coronavirus Infections; Pneumonia; Pneumonia, Viral
• Other Study ID Numbers: Tsunami

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No