Therapeutic Use of Convalescent Plasma in the Treatment of Patients With Moderate to Severe COVID-19

COVID-19 Clinical Trial

Official title:

A Prospective, Randomized, Placebo-controlled, Double-blinded, Phase III Clinical Trial of the Therapeutic Use of Convalescent Plasma in the Treatment of Patients With Moderate to Severe COVID-19

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04516811
• Other study ID #: PROTECT-Patient trial
• Status: Recruiting
• Phase: Phase 3
• Start date: September 21, 2020
• Est. completion date: July 31, 2022

Study information

• Verified date: September 2020
• Source: South African National Blood Service
• Contact: Cynthia Nyoni
• Phone: +27117619279
• Email: Cynthia.Nyoni[@]sanbs.org.za
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A prospective, randomized, placebo-controlled, double-blinded, phase III clinical trial of the therapeutic use of convalescent plasma in the treatment of patients with moderate to severe COVID-19

Description:

Full Title: A prospective, randomized, placebo-controlled, double-blinded, phase III clinical trial of the therapeutic use of convalescent plasma in the treatment of patients with moderate to severe COVID-19.

Short Title: PROTECT-Patient study

Aim: Assess the safety and efficacy of COVID-19 convalescent plasma (CCP) as a therapeutic treatment for hospitalised patients with moderate to severe COVID-19

Study Design: Randomised, double-blinded, placebo-controlled, phase III clinical trial

Intervention: Randomised 1:1 to either CCP plus standard of care (SOC) or to SOC plus placebo (200 mL normal saline)

Active Agent: A single unit of approximately 200-250 mL of CCP that contains anti-SARS-CoV-2 collected by plasmapheresis from a volunteer who recovered from COVID19 with SOC as determined by local practice and guidelines.

Placebo: A single unit of 200 mL normal saline with SOC as determined by local practice and guidelines

Sample Size: 600

Study Population: Consenting adult inpatients with moderate to severe COVID-19, not requiring invasive ventilation, who are admitted to a participating public or private sector hospital and who are not enrolled in another COVID-19 treatment trial.

Settings: Participating public and private sector hospitals in South Africa

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: July 31, 2022
• Est. primary completion date: December 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Laboratory confirmed SARS-CoV-2 by positive RT-PCR on any respiratory sample;

• Age = 18 years;

• Require hospital admission for COVID-19 pneumonia as defined by the presence of pulmonary infiltrates on chest x-ray;

• Moderate to severe Covid-19 disease, defined as: SpO2 = 93% on room air; plus requiring non-invasive oxygen therapy (WHO R&D BOSCI 4 or 5

• Signed informed consent;

• Pregnant women will be allowed to participate.

Exclusion Criteria:

• Current participation in another therapeutic clinical trial for COVID-19;

• Invasive mechanical ventilation;

• Expected survival < 24 hours based on clinical assessment (however, the study does not exclude critically ill patients who are not, due to resource limitations, candidates for critical care admission and/or mechanical ventilation);

• Known hypersensitivity to immunoglobulin or any components of the formulation;

Related Conditions & MeSH terms

• Coronavirus Infections
• COVID-19
• SARS-CoV-2 Infection
• Severe Acute Respiratory Syndrome
• Severe Acute Respiratory Syndrome Coronavirus 2

Intervention

Biological:
• COVID-19 convalescent plasma (CCP) plus standard of care (SOC)
A single unit of approximately 200-250 mL of CCP that contains anti-SARS-CoV-2 collected by plasmapheresis from a volunteer who recovered from COVID19 with SOC as determined by local practice and guidelines.
• Standard of care (SOC) plus placebo
A single unit of 200 mL normal saline with SOC as determined by local practice and guidelines

Locations

Country	Name	City	State
South Africa	Universitas Hospital	Bloemfontein	Free State
South Africa	Mitchells Plain Hospital	Cape Town	Western Cape

Sponsors (1)

Lead Sponsor	Collaborator
South African National Blood Service

Country where clinical trial is conducted

South Africa, 

References & Publications (7)

Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020 Apr;5(4):536-544. doi: 10.1038/s41564-020-0695-z. Epub 2020 Mar 2. — View Citation

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum in: Lancet. 2020 Jan 30;:. — View Citation

Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW; the Northwell COVID-19 Research Consortium, Barnaby DP, Becker LB, Chelico JD, Cohen SL, Cookingham J, Coppa K, Diefenbach MA, Dominello AJ, Duer-Hefele J, Falzon L, Gitlin J, Hajizadeh N, Harvin TG, Hirschwerk DA, Kim EJ, Kozel ZM, Marrast LM, Mogavero JN, Osorio GA, Qiu M, Zanos TP. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 May 26;323(20):2052-2059. doi: 10.1001/jama.2020.6775. Erratum in: JAMA. 2020 May 26;323(20):2098. — View Citation

Thorlund K, Dron L, Park J, Hsu G, Forrest JI, Mills EJ. A real-time dashboard of clinical trials for COVID-19. Lancet Digit Health. 2020 Jun;2(6):e286-e287. doi: 10.1016/S2589-7500(20)30086-8. Epub 2020 Apr 24. — View Citation

Yuen KS, Ye ZW, Fung SY, Chan CP, Jin DY. SARS-CoV-2 and COVID-19: The most important research questions. Cell Biosci. 2020 Mar 16;10:40. doi: 10.1186/s13578-020-00404-4. eCollection 2020. — View Citation

Zhang L, Liu Y. Potential interventions for novel coronavirus in China: A systematic review. J Med Virol. 2020 May;92(5):479-490. doi: 10.1002/jmv.25707. Epub 2020 Mar 3. — View Citation

Zu ZY, Jiang MD, Xu PP, Chen W, Ni QQ, Lu GM, Zhang LJ. Coronavirus Disease 2019 (COVID-19): A Perspective from China. Radiology. 2020 Aug;296(2):E15-E25. doi: 10.1148/radiol.2020200490. Epub 2020 Feb 21. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Improvement	Proportion of participants with successful treatment outcome, defined as clinical improvement (= 2 points on WHO R&D BOSCI 1) by Day 28 post-randomisation.	Day 28
Secondary	Adverse Events of special interest	1. Proportion of participants with adverse events of special interest (Transfusion-Associated Circulatory Overload (TACO); Transfusion-Related Acute Lung Injury (TRALI); allergic transfusion reaction).	Day 28
Secondary	Serious Adverse Events	2. Proportion of participants with serious adverse events.	Day 28
Secondary	Survival	3. Proportion of participants surviving at Day 28 post-randomisation.	Day 28
Secondary	Invasive mechanical ventilation	4. Proportion of participants requiring invasive mechanical ventilation.	Day 28
Secondary	Disease severity	5. Proportion of participants with moderate and severe ARDS.	Day 28
Secondary	Time to outcomes of interest	6. Time from randomization to death, clinical improvement, ICU admission, and invasive mechanical ventilation.	Day28
Secondary	Length of stay meausures	7. Duration of hospitalisation, ICU stay, and mechanical ventilation in survivors.	Day28
Secondary	SARS-CoV PCR	8. Proportion negative SARS-CoV-2 PCR at Day 28; time to viral clearance (PCR-negativity); change in SARS-CoV-2 PCR Ct value.	Day28
Secondary	Inflammatory markers	9. Proportion with and time to normalisation of inflammatory markers, including CRP, lymphocyte count, D-dimer, ferritin.	Day28
Secondary	Radiography	10. Worsening of radiographic abnormalities.	Day28
Secondary	Fever & Hypoxia	11. Proportion with and time to resolution of fever and hypoxia.	Day28
Secondary	patients with HIV infection and other comorbidities	12. Proportion of patients with HIV infection and other comorbidities (obesity, diabetes, hypertension) with primary efficacy outcome.	Day 28
Secondary	Timing of IP & Efficacy Outcome	13. Relationship between timing of transfusion from symptom onset and primary efficacy outcome.	Day 28
Secondary	Neutralising Ab	14. Relationship between convalescent plasma neutralizing antibody titers and primary efficacy outcome	Day28
Secondary	SARS CoV Antibody titre	15. Comparison of anti-SARS-CoV-2 titer dynamics between treatment arms	Day28