Convalescent Plasma Compared to the Best Available Therapy for the Treatment of SARS-CoV-2 Pneumonia

Coronavirus Infection Clinical Trial

— COP-COVID-19  

Official title:

Phase II, Randomized, Double-blind, Controlled Clinical Trial Evaluating the Efficacy and Safety of Plasma From Patients Cured of COVID-19 Compared to the Best Available Therapy in Subjects With SARS-CoV-2 Pneumonia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04358783
• Other study ID #: IF20-00002
• Status: Completed
• Phase: Phase 2
• Start date: April 27, 2020
• Est. completion date: May 1, 2021

Study information

• Verified date: May 2021
• Source: Hospital Universitario Dr. Jose E. Gonzalez
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In early December 2019, cases of pneumonia of unknown origin were identified in Wuhan, China. The causative virus was called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The World Health Organization (WHO) has recently declared coronavirus disease 2019 (COVID-19) a public health emergency of international concern. According to the World Health Organization (WHO), the management of COVID-19 has focused primarily on infection prevention, detection and patient monitoring. However, there is no vaccine or specific treatment for SARS-CoV-2 due to the lack of evidence. Treatment options currently include broad-spectrum antiviral drugs but the efficacy and safety of these drugs is still unknown. Convalescent plasma has previously been used to treat various outbreaks of other respiratory infections; however, it has not been shown to be effective in all the diseases studied. Therefore, clinical trials are required to demonstrate its safety and efficacy in patients with VIDOC-19. The present work seeks to determine the mortality from any cause up to 14 days after plasma randomization of patients cured of COVID-19 compared to the Best Available Therapy in subjects with SARS-CoV-2 pneumonia. This is a 2:1 randomized, double-blind, single-center, phase 2, controlled clinical trial (plasma: best available therapy) for the treatment of SARS-CoV-2 pneumonia.

Description:

Randomized clinical trial comparing convalescent plasma to best available therapy (BAT) for the treatment of severely ill and critically ill patient with COVID-19: Patients will be electronically randomized 2:1 (plasma vs BAT) in a double blind fashion. Patients with SARS-CoV-2 PCR confirmed infection with pulmonary infiltrates and hypoxemia will be screened and invited to participate. Primary outcomes will be early all-cause mortality, and secondary outcomes will include all cause in hospital mortality, length of mechanical ventilation and hospital stay, time to PAO2 >200, progression of pulmonary infiltrates, antibody titers and time to negative PCR detection

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: May 1, 2021
• Est. primary completion date: May 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Men or women =18 years. If you are a woman of childbearing age, you must agree to practice abstinence or to use an effective method of contraception during the study period.

2. Vascular access suitable for administration of hemocomponents.

3. SARS-CoV-2 positive RT-PCR.

4. Negative pregnancy test in case of a woman of reproductive age

5. Signing of evidentiary document of informed consent.

6. Hospital admission for SARS-CoV-2 pneumonia with supplemental oxygen requirements.

7. Subjects who access the storage of biological samples for future examination.

Exclusion Criteria:

1. Respiratory rate >30 RPM, SO2 <93%, PaO2/FiO2 <200 despite intervention with oxygen therapy after 60 minutes of hospitalization.

2. New alteration of the state of alert that does not revert after interventions 60 minutes after admission to hospital.

3. PAM = 65mmHg despite initial resuscitation on arrival at the centre.

4. Pregnant or breastfeeding patients.

5. Patients that the investigators consider inappropriate to participate in the clinical trial

6. Contraindication to transfusion or history of previous severe reaction to blood products.

7. Have received any blood products in the last 120 days.

Related Conditions & MeSH terms

• Coronavirus Infection
• Coronavirus Infections
• Pneumonia

Intervention

Biological:
• Plasma
The plasma unit will be fractionated in 200 mL aliquots for storage at -80°C until use. After thawing, it shall be administered in a single 200 mL dose to subjects who are randomized to that arm.

Other:
• Best Available Therapy
It shall include, but not be limited to, oxygen therapy by means of a nasal cannula; high-flow nasal cannula; invasive or non-invasive mechanical ventilation; intravenous hydration; antibiotic therapy; thrombus prophylaxis; pain and fever management.

Locations

Country	Name	City	State
Mexico	Hospital Universitario José E. Gonzalez	Monterrey	Nuevo Leon

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitario Dr. Jose E. Gonzalez

Country where clinical trial is conducted

Mexico, 

References & Publications (21)

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Disease C. Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease ( COVID-19 ). CDC. 2020;2019:4-6.

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28. — View Citation

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Heymann DL, Shindo N; WHO Scientific and Technical Advisory Group for Infectious Hazards. COVID-19: what is next for public health? Lancet. 2020 Feb 22;395(10224):542-545. doi: 10.1016/S0140-6736(20)30374-3. Epub 2020 Feb 13. — View Citation

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Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR; Convalescent Plasma Study Group. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 2015 Jan 1;211(1):80-90. doi: 10.1093/infdis/jiu396. Epub 2014 Jul 16. Review. — View Citation

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Sahr F, Ansumana R, Massaquoi TA, Idriss BR, Sesay FR, Lamin JM, Baker S, Nicol S, Conton B, Johnson W, Abiri OT, Kargbo O, Kamara P, Goba A, Russell JB, Gevao SM. Evaluation of convalescent whole blood for treating Ebola Virus Disease in Freetown, Sierra Leone. J Infect. 2017 Mar;74(3):302-309. doi: 10.1016/j.jinf.2016.11.009. Epub 2016 Nov 17. — 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

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* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early all-cause mortality	any cause mortality during the first 14 days of treatment	14 days
Secondary	Time in days for SARS-CoV-2 RT-PCR negatives	(48-hour sampling interval from day 3 of hospitalization to two consecutive negatives).	90 days
Secondary	The serum anti-SARS-CoV-2 antibody titres	In subjects of both arms at day 0, 3, 7, 14 and 90.	90 days
Secondary	Detection of serum antibodies	Comparison of anti-SARS-CoV-2 antibody titers	days 0, 3, 7, 14 and 90.