Convalescent Plasma Trial in COVID -19 Patients

COVID-19 Clinical Trial

Official title:

Use of Convalescent Plasma Therapy for COVID-19 Patients With Hypoxia: a Prospective Randomized Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04356534
• Other study ID #: BDF/R&REC/2020-423
• Status: Completed
• Phase: N/A
• Start date: April 19, 2020
• Est. completion date: July 9, 2020

Study information

• Verified date: July 2020
• Source: Royal College of Surgeons in Ireland - Medical University of Bahrain
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Plasma therapy using convalescent plasma has been shown to be effective in severe acute respiratory syndrome, Ebola virus infection and in H1N1 influenza. More recently there has been a report of the use of convalescent plasma in the treatment of 5 ventilated COVID-19 patients with the suggestion of expedited recovery as the patients improved 1 week after the transfusion. However, this was not a clinical trial and the patients were on other antiviral medication.; therefore, there is a need to undertake such a trial to see if deploying plasma with SARS-CoV-2 neutralizing antibody has utility in managing patients infected with COVID-19 in respiratory distress. The objective of this pilot study is to compare plasma therapy using convalescent plasma with antibody against SARS-CoV-2 to usual supportive therapy in COVID-19 patients with pneumonia and hypoxia, and to determine if the clinical course is improved. The difference between groups will allow an effect size to be determined for a definitive clinical trial.

Description:

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has developed into a pandemic with serious global public health and economic sequelae. As of March 30, 2020, over 750,000 cases have been confirmed worldwide leading to over 34,000 deaths (https://coronavirus.jhu.edu/map.html). There is no current vaccine available, but there have been a number of reports of medication such as hydroxychloroquine having antiviral properties with efficacy against SARS-CoV-2. Plasma therapy using convalescent plasma has been shown to be effective in severe acute respiratory syndrome, Ebola virus infection and in H1N1 influenza. More recently there has been a report of the use of convalescent plasma in the treatment of 5 ventilated COVID-19 patients with the suggestion of expedited recovery as the patients improved 1 week after the transfusion. However, this was not a clinical trial and the patients were on other antiviral medication; therefore, there is a need to undertake such a trial to see if deploying plasma with SARS-CoV-2 neutralizing antibody has utility in managing patients infected with COVID-19 in respiratory distress. The objective of this pilot study is to compare plasma therapy using convalescent plasma with antibody against SARS-CoV-2 to usual supportive therapy in COVID-19 patients with pneumonia and hypoxia, and to determine if the clinical course is improved. The difference between groups will allow an effect size to be determined for a definitive clinical trial Could using convalescent plasma transfusion, from recovered COVID19 patients with antibody against COVID-19 be beneficial in treatment of COVID19 patients with hypoxia and pneumonia, in order to avoid or delay the need for invasive ventilation? This is a prospective, interventional and randomized open label trial involving 40 patients with COVID-19 who are in respiratory distress, with the criteria that all require oxygen therapy and have radiological evidence of pneumonia, 20 of whom will receive a single transfusion of convalescent patient plasma plus routine care, compared to 20 COVID-19 patients who will receive routine care alone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 9, 2020
• Est. primary completion date: June 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

• COVID-19 diagnosis
• Hypoxia, (Oxygen saturation of less than or equal 92% or PO2 < 60mmHg on arterial blood gas analysis) and patient requiring oxygen therapy
• Evidence of infiltrates on Chest Xray or CT scan
• Able to give informed consent
• Patients between the ages of 21 and above with no upper age.

Exclusion Criteria:

• Patients with mild disease not requiring oxygen therapy
• Patients with normal CXR & CT scan
• Patients requiring ventilatory support
• Patients with a history of allergy to plasma, sodium citrate or methylene blue
• Patients with a history of autoimmune disease or selective IGA deficiency.

Related Conditions & MeSH terms

• COVID-19
• SARS-CoV 2

Intervention

Other:
• plasma therapy using convalescent plasma with antibody against SARS-CoV-2
convalescent patient plasma plus routine local standard of care
• Routine care for COVID-19 patients
local standard of care which include antivirals and supportive care

Locations

Country	Name	City	State
Bahrain	Royal College of Surgeons in Ireland - Bahrain	Manama

Sponsors (4)

Lead Sponsor	Collaborator
Royal College of Surgeons in Ireland - Medical University of Bahrain	Bahrain Defence Force Hospital, Mohammed Bin Khalifa Bin Sulman Al Khalifa Cardiac Centre, Awali, Salmaniya Medical Complex

Country where clinical trial is conducted

Bahrain, 

References & Publications (12)

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Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, Liao X, Gu Y, Cai Q, Yang Y, Shen C, Li X, Peng L, Huang D, Zhang J, Zhang S, Wang F, Liu J, Chen L, Chen S, Wang Z, Zhang Z, Cao R, Zhong W, Liu Y, Liu L. Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. Engineering (Beijing). 2020 Oct;6(10):1192-1198. doi: 10.1016/j.eng.2020.03.007. Epub 2020 Mar 18. — View Citation

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Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther. 2020;14(1):58-60. doi: 10.5582/ddt.2020.01012. — View Citation

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honoré S, Colson P, Chabrière E, La Scola B, Rolain JM, Brouqui P, Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Jul;56(1):105949. doi: 10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20. — View Citation

Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, Liu R, Watt CL, Chan WM, Lai KY, Koo CK, Buckley T, Chow FL, Wong KK, Chan HS, Ching CK, Tang BS, Lau CC, Li IW, Liu SH, Chan KH, Lin CK, Yuen KY. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011 Feb 15;52(4):447-56. doi: 10.1093/cid/ciq106. Epub 2011 Jan 19. — View Citation

Knol MJ, Groenwold RH, Grobbee DE. P-values in baseline tables of randomised controlled trials are inappropriate but still common in high impact journals. Eur J Prev Cardiol. 2012 Apr;19(2):231-2. — View Citation

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

Senn S. Testing for baseline balance in clinical trials. Stat Med. 1994 Sep 15;13(17):1715-26. — View Citation

Senn SJ. Covariate imbalance and random allocation in clinical trials. Stat Med. 1989 Apr;8(4):467-75. — 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

Soo YO, Cheng Y, Wong R, Hui DS, Lee CK, Tsang KK, Ng MH, Chan P, Cheng G, Sung JJ. Retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in SARS patients. Clin Microbiol Infect. 2004 Jul;10(7):676-8. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Requirement for invasive ventilation	Could the plasma therapy avoid or delay the need for invasive ventilation	through study completion up to 28 days
Secondary	Change in viral clearance	Through the use of CT values	through study completion up to 28 days
Secondary	Radiological change	Chest Xray	through study completion up to 28 days
Secondary	Change in white cell count	As a measure of a change in inflammation	through study completion up to 28 days
Secondary	C reactive protein measurement	A change in C reactive protein as a measure of a change in inflammation	through study completion up to 28 days
Secondary	lactate dehydrogenase measurement	A change in lactate dehydrogenase as a measure of an improvement in the severity of the disease process	through study completion up to 28 days
Secondary	Procalcitonin measurement	A change in procalcitonin as a measure of an improvement in the severity of the disease process	through study completion up to 28 days
Secondary	D Dimer measurement	A change in D Dimer as a measure of an improvement in the severity of the disease process	through study completion up to 28 days
Secondary	Ferritin measurement	A change in Ferritin as a measure of an improvement in the severity of the disease process	through study completion up to 28 days
Secondary	Troponin T measurement	A change in troponin T as a measure of an improvement in the severity of the disease process	through study completion up to 28 days
Secondary	Brain naturetic peptide measurement	A change in brain naturetic peptide as a measure of an improvement in the severity of the disease process	through study completion up to 28 days
Secondary	Mortality rate	Mortality rate due to COVID-19	Up to 28 days of the study