Convalescent Plasma for Severe COVID-19 Patients

Covid19 Clinical Trial

— PLACOVID  

Official title:

Convalescent Plasma for Severe COVID-19 Patients: a Randomized, Open-label, Phase 3 Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04547660
• Other study ID #: 2020-0158
• Status: Completed
• Phase: Phase 3
• Start date: July 16, 2020
• Est. completion date: January 7, 2021

Study information

• Verified date: February 2021
• Source: Hospital de Clinicas de Porto Alegre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a randomized, open-label, phase 3 clinical trial on the use of convalescent plasma for severe COVID-19 patients. In this research, we are going to assess efficacy and safety of convalescent plasma in the treatment of severely compromised COVID-19 patients. Convalescent plasma will be collected from recovered COVID-19 patients, who will be recruited as plasma donors and will be submitted to apheresis (with minimum interval of 14 days) to obtain two aliquots of 300 ml of convalescent plasma, which will be frozen at -80 and stored at -20 to -30 degrees Celsius. Enrolled patients will be randomized based on a concealed sequential allocation list by an independent researcher which will not be aware of patients characteristics, and stratified by COVID-19 severity (severe or life-threatening). There will be two arms of study, intervention or control group, and patients will be followed up for the next 28 days for clinical and laboratory outcomes such as improvement of disease status (measured by a 6-point ordinal severity scale); mechanical ventilation, intensive care unit (ICU) and total hospital stay period; cytokine levels (IL-6 and TNF-alfa) and several inflammatory, cellular injury and coagulation parameters. Intervention was conceived as two infusions of 300 ml of convalescent plasma, 2 days apart. Control group will receive full supportive treatment but will not be allowed to receive other investigational drugs. Sample size was calculated to a total of 160 patients, with a 1:1 randomization proportion between groups. This amount would be capable to detect an 18% or higher difference in the proportion of clinical improvement at 28 days of enrollment between intervention and control groups, with an alfa error of 0.05 and a statistical power of 0.8.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: January 7, 2021
• Est. primary completion date: January 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age equal to or greater than 18 yers;

2. Diagnosis of SARS-CoV-2 infection through nasal cavity or oropharynx swab RT-PCR;

3. 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;

4. Onset of symptoms in a period not exceeding 14 days.

Exclusion Criteria:

1. Impossibility for any reason to perform the first plasma infusion within 14 days of the onset of symptoms;

2. Use of immunosuppressants for other underlying diseases, except corticosteroids for the SARS-CoV-2, in the last 30 days before enrollment;

3. Pregnancy;

4. History of serious adverse reactions such as transfusion anaphylaxis;

5. Participation in another interventional clinical trial;

6. Disagreement of attending physician;

7. Disagreement of the patient or legal representative to participate in the study.

Related Conditions & MeSH terms

• Covid19

Intervention

Biological:
• Convalescent Plasma
Fresh frozen plasma collected by apheresis from recovered COVID-19 patients added to best supportive care.

Other:
• Best Supportive Care
Any form of ventilatory support, extracorporeal membrane oxygenation, steroids, antibiotics and other supportive measures except for investigational interventions.

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul

Sponsors (3)

Lead Sponsor	Collaborator
Hospital de Clinicas de Porto Alegre	Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil, Instituto Cultural Floresta

Country where clinical trial is conducted

Brazil, 

References & Publications (4)

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. — View Citation

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. Erratum in: JAMA. 2020 Aug 4;324(5):519. — View Citation

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. — 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	6-point ordinal scale proportion at 14 days	Proportions of individuals classified in each 6-point ordinal scale strata	14 days from randomization
Secondary	6-point ordinal scale proportion at 28 days	Proportions of individuals classified in each 6-point ordinal scale strata	28 days from randomization
Secondary	Overall mortality	Death from any cause after randomization	14 days
Secondary	Overall mortality	Death from any cause after randomization	28 days
Secondary	Days alive and free of respiratory support (DAFOR28)	Days free of respiratory support during follow up	28 days
Secondary	Mechanical ventilation	Duration of invasive ventilatory support (for those who received mechanical ventilation)	28 days
Secondary	PaO2/FiO2 ratio	PaO2/FiO2 ratio at 7 days of follow up	At the 7th day of randomization
Secondary	Hospital stay	Time from randomization to hospital discharge (for 28-day survivors)	28 days
Secondary	Lactate Dehydrogenase	LDH (U/L)	Randomization day, Day 3, Day 7 and Day 14
Secondary	Troponin I	Troponin I (pg/mL)	Randomization day, Day 3, Day 7 and Day 14
Secondary	C Reactive Protein	CRP (mg/L)	Randomization day, Day 3, Day 7 and Day 14
Secondary	D-Dimers	D-Dimers (mcg/mL)	Randomization day, Day 3, Day 7 and Day 14
Secondary	Fibrinogen	Fibrinogen (mg/dL)	Randomization day, Day 3, Day 7 and Day 14
Secondary	Prothrombin Time (PT)	PT (seconds)	Randomization day, Day 3, Day 7 and Day 14
Secondary	Activated Partial Thromboplastin Time (APTT)	APTT (seconds)	Randomization day, Day 3, Day 7 and Day 14
Secondary	Tumor Necrosis Factor Alfa (TNF-Alfa)	TNF-Alfa (pg/mL)	Randomization day, Day 3, Day 7 and Day 14
Secondary	Interleukin-6 (IL-6)	IL-6 (pg/mL)	Randomization day, Day 3, Day 7 and Day 14
Secondary	RT-PCR	Nasal and Oropharyngeal Swab RT-PCR	At the 7th day of randomization (or at hospital discharge if earlier than 7 days)
Secondary	Sequential Organ Failure Assessment (SOFA) score	SOFA score at 7 days of randomization (ranges from 0 to 24, prognosis worsens with higher score values)	At the 7th day of randomization
Secondary	National Early Warning Score 2 (NEWS) 2	Change in NEWS 2 from randomization at 7 days and 14 days (ranges from 0 to 20, prognosis worsens with higher score values)	7 and 14 days of randomization
Secondary	Safety and Adverse Events	CTCAE grade 3-4 events during follow up	28 days