Convalescent Plasma for Severe COVID-19 Patients

NCT04547660 | Completed Phase 3 DMC

• 1 other identifier: 2020-0158
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Plasma, the supernatant part of blood, contains a variety of different proteins, including immunoglobulins. These proteins, also called antibodies, are directed to previous foreign infecting organisms, such as virus, bacteria or parasites. Patients recovering from SARS-Cov-2 infection may develop protective antibodies which can prevent reinfection with the same agent or similar organisms with shared molecular structures. Those antibodies may be transferred to other patients through collection of such convalescent plasma from recovered donors and its transfusion to ill patients. In this research, the primary hypothesis is that those antibodies can exert passive immunization and help ameliorate symptoms from COVID-19 (Coronavirus Disease 2019), resulting in higher clinical improvement rates at day 28, especially when administered early in the infection course.

Conditions

Covid19

Outcome Measures

Primary Outcomes (1)

• Clinical improvement

  Improvement of 2 points from randomization in a 6-point ordinal severity scale (6 points, death; 5 points, hospitalization plus extracorporeal membrane oxygenation (ECMO) or invasive mechanical ventilation; 4 points, hospitalization plus noninvasive ventilation or high-flow supplemental oxygen; 3 points, hospitalization plus supplemental oxygen (not high-flow or noninvasive ventilation); 2 points, hospitalization with no supplemental oxygen; 1 point, hospital discharge)

  28 days

Secondary Outcomes (21)

• 6-point ordinal scale proportion at 14 days

  14 days from randomization

• 6-point ordinal scale proportion at 28 days

  28 days from randomization

• Overall mortality

  14 days

• Overall mortality

  28 days

• Days alive and free of respiratory support (DAFOR28)

  28 days

Study Arms (2)

Convalescent Plasma

EXPERIMENTAL

Transfusion of 2 aliquots of 300 ml of frozen convalescent plasma, 2 days apart, thawed at 37 degrees Celsius before infusion. Best supportive care except for investigational interventions.

Biological: Convalescent Plasma; Other: Best Supportive Care

Best Supportive Care

ACTIVE COMPARATOR

Any form of ventilatory support, extracorporeal membrane oxygenation, steroids, antibiotics and other supportive measures except for investigational interventions.

Other: Best Supportive Care

Interventions

Convalescent Plasma BIOLOGICAL

Fresh frozen plasma collected by apheresis from recovered COVID-19 patients added to best supportive care.

Convalescent Plasma

Best Supportive Care OTHER

Any form of ventilatory support, extracorporeal membrane oxygenation, steroids, antibiotics and other supportive measures except for investigational interventions.

Also known as: Standard Treatment

Best Supportive Care; Convalescent Plasma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age equal to or greater than 18 yers;
• Diagnosis of SARS-CoV-2 infection through nasal cavity or oropharynx swab RT-PCR;
• Severe COVID-19 defined by the presence of at least 1 of the following:
• A. Respiratory rate\> 30 breaths per minute in room air; B. Oxygen saturation (O2) ≤93% in room air; C. PaO2 / FiO2 ratio ≤300; D. Need for supplemental O2 to maintain O2 saturation\> 95%; E. Need for therapy with supplemental O2 by high flow catheter or non-invasive ventilation or invasive mechanical ventilation;
• Onset of symptoms in a period not exceeding 14 days.

You may not qualify if:

• Impossibility for any reason to perform the first plasma infusion within 14 days of the onset of symptoms;
• Use of immunosuppressants for other underlying diseases, except corticosteroids for the SARS-CoV-2, in the last 30 days before enrollment;
• Pregnancy;
• History of serious adverse reactions such as transfusion anaphylaxis;
• Participation in another interventional clinical trial;
• Disagreement of attending physician;
• Disagreement of the patient or legal representative to participate in the study.

Sponsors & Collaborators

• Hospital de Clinicas de Porto Alegre: lead
• Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil: collaborator
• Instituto Cultural Floresta: collaborator

Study Sites (1)

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Related Publications (4)

• Salazar E, Perez KK, Ashraf M, Chen J, Castillo B, Christensen PA, Eubank T, Bernard DW, Eagar TN, Long SW, Subedi S, Olsen RJ, Leveque C, Schwartz MR, Dey M, Chavez-East C, Rogers J, Shehabeldin A, Joseph D, Williams G, Thomas K, Masud F, Talley C, Dlouhy KG, Lopez BV, Hampton C, Lavinder J, Gollihar JD, Maranhao AC, Ippolito GC, Saavedra MO, Cantu CC, Yerramilli P, Pruitt L, Musser JM. Treatment of Coronavirus Disease 2019 (COVID-19) Patients with Convalescent Plasma. Am J Pathol. 2020 Aug;190(8):1680-1690. doi: 10.1016/j.ajpath.2020.05.014. Epub 2020 May 27.

  PMID: 32473109 BACKGROUND

• Li L, Zhang W, Hu Y, Tong X, Zheng S, Yang J, Kong Y, Ren L, Wei Q, Mei H, Hu C, Tao C, Yang R, Wang J, Yu Y, Guo Y, Wu X, Xu Z, Zeng L, Xiong N, Chen L, Wang J, Man N, Liu Y, Xu H, Deng E, Zhang X, Li C, Wang C, Su S, Zhang L, Wang J, Wu Y, Liu Z. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial. JAMA. 2020 Aug 4;324(5):460-470. doi: 10.1001/jama.2020.10044.

  PMID: 32492084 BACKGROUND

• 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.

  PMID: 32219428 BACKGROUND

• Joyner MJ, Bruno KA, Klassen SA, Kunze KL, Johnson PW, Lesser ER, Wiggins CC, Senefeld JW, Klompas AM, Hodge DO, Shepherd JRA, Rea RF, Whelan ER, Clayburn AJ, Spiegel MR, Baker SE, Larson KF, Ripoll JG, Andersen KJ, Buras MR, Vogt MNP, Herasevich V, Dennis JJ, Regimbal RJ, Bauer PR, Blair JE, van Buskirk CM, Winters JL, Stubbs JR, van Helmond N, Butterfield BP, Sexton MA, Diaz Soto JC, Paneth NS, Verdun NC, Marks P, Casadevall A, Fairweather D, Carter RE, Wright RS. Safety Update: COVID-19 Convalescent Plasma in 20,000 Hospitalized Patients. Mayo Clin Proc. 2020 Sep;95(9):1888-1897. doi: 10.1016/j.mayocp.2020.06.028. Epub 2020 Jul 19.

  PMID: 32861333 BACKGROUND

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Leo Sekine, PhD

  Hospital de Clínicas de Porto Alegre

  PRINCIPAL INVESTIGATOR

• Alexandre P Zavascki, PhD

  Federal University of Rio Grande do Sul

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcomes will be analyzed by blinded investigators. Group allocation will not be disclosed during statistical analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, open-label, phase 3, comparing best supportive care (BSC, no investigational drugs allowed) and convalescent plasma, along BSC.

Study Record Dates

• First Submitted: September 9, 2020
• First Posted: September 14, 2020
• Study Start: July 16, 2020
• Primary Completion: January 7, 2021
• Study Completion: January 7, 2021
• Last Updated: February 9, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)