Anti COVID-19 Convalescent Plasma Therapy

COVID 19 Clinical Trial

Official title:

Anti COVID-19 Convalescent Plasma Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04345679
• Other study ID #: AntiCOVID19ORT
• Status: Recruiting
• Phase: Early Phase 1
• Start date: April 14, 2020
• Est. completion date: September 1, 2021

Study information

• Verified date: February 2021
• Source: Orthosera Kft.
• Contact: Eszter Fodor, medical doctor
• Phone: +36306640494
• Email: eszter.fodor[@]orthosera.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Why is the research needed? The pandemic known as COVID-19 is now spreading across the world with currently (April 10, 2020) more than 1 115 530 active cases and 96 791 deaths. In most affected countries the current goal is to 'flatten the curve' of the epidemic since there is no health care system that is able to treat an extremely high volume of patients all at once. There is a need for immediately applicable treatments for the patients at highest risk, which gains time until targeted therapies become available. A key feature in the pathomechanism of the disease is that the virus elicits an immunological over-reaction in the human body termed 'cytokine storm'. In susceptible patients this hyper-inflammation itself is a significant burden and may even inhibit the body to generate antibodies against the virus in adequate quantities. Therefore, identifying the subset of patients with excess cytokine response and supplementing them with convalescent plasma from recovered donors may be a life-saving treatment option.

What is our study about? In light of recent promising data on plasma therapy in the treatment of COVID-19 and other viral epidemics, there is a need for better understanding the cytokine response to the virus in order to better characterize the target population for convalescent plasma therapy.

Our hypothesis is that convalescent plasma transfusion from healthy donors who recovered from SARS CoV-2 is able to reduce the cytokine storm in addition to replenish the patient's own antibodies in the acutely infected phase of the disease.

A plasmapheresis donation of 400ml will be performed in subjects who recovered from COVID-19 and who are otherwise eligible for plasma donation. The sample will be tested for anti-SARS CoV-2 neutralizing antibody titers and those that reach the level of 1:320 will be processed for transfusion at the Hungarian National Transfusion Service.

Recipients will be COVID-19 patients requiring hospitalization regardless of the severity of the disease or other co-morbidities. A blood-type matched transfusion of 200 ml convalescent plasma will be infused in a single sitting through an iv. infusion of 4 hours.

Recipients will be followed up at days 1, 3,7,12, 17, 28 for clinical symptoms, antibody levels and cytokine response.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: September 1, 2021
• Est. primary completion date: June 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria for blood donors :

• age : >18 and <60 years

• body weight : >50 kg

• confirmed previous SARS CoV-2 infection

• 2 negative SARS CoV-2 test result

• written informed consent

• neutralizing antibody titer min. 1 : 120

Exclusion criteria for blood donors :

• age : <18 or >60 years

• female subjects who are pregnant

• HIV1,2 hepatitis B,C or syphilis infection

to minimize the transfusional side effects our aim is to include mostly male donors.

Inclusion criteria for patients/recipients :

• age : >18 years

• admitted to hospital due to SARS CoV-2 infection

• written informed consent

Exclusion criteria for patients/recipients :

• age : <18 years

• female subjects who are pregnant or breastfeeding

• patients with prior allergic reaction to transfusion

• patients who received in the past 30 days immunoglobulin therapy

Related Conditions & MeSH terms

• COVID 19

Intervention

Biological:
• anti-SARS-CoV-2 convalescent plasma
Infusion of one unit of anti-SARS-CoV-2 convalescent plasma ~200 mL over 4 hours

Locations

Country	Name	City	State
Hungary	Semmelweis University's Department of Pulmonology	Budapest

Sponsors (5)

Lead Sponsor	Collaborator
Orthosera Kft.	Humán Bioplazma Kft - Kedrion, Hungarian National Blood Service, Semmelweis University, University of Pecs

Country where clinical trial is conducted

Hungary, 

References & Publications (7)

Arabi Y, Balkhy H, Hajeer AH, Bouchama A, Hayden FG, Al-Omari A, Al-Hameed FM, Taha Y, Shindo N, Whitehead J, Merson L, AlJohani S, Al-Khairy K, Carson G, Luke TC, Hensley L, Al-Dawood A, Al-Qahtani S, Modjarrad K, Sadat M, Rohde G, Leport C, Fowler R. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus. 2015 Nov 19;4:709. doi: 10.1186/s40064-015-1490-9. eCollection 2015. — View Citation

Belyakov IM, Hel Z, Kelsall B, Kuznetsov VA, Ahlers JD, Nacsa J, Watkins DI, Allen TM, Sette A, Altman J, Woodward R, Markham PD, Clements JD, Franchini G, Strober W, Berzofsky JA. Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaques. Nat Med. 2001 Dec;7(12):1320-6. — 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

Kardos D, Marschall B, Simon M, Hornyák I, Hinsenkamp A, Kuten O, Gyevnár Z, Erdélyi G, Bárdos T, Paukovits TM, Magos K, Béres G, Szenthe K, Bánáti F, Szathmary S, Nehrer S, Lacza Z. Investigation of Cytokine Changes in Osteoarthritic Knee Joint Tissues in Response to Hyperacute Serum Treatment. Cells. 2019 Aug 3;8(8). pii: E824. doi: 10.3390/cells8080824. — View Citation

Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. — View Citation

Nacsa J, Edghill-Smith Y, Tsai WP, Venzon D, Tryniszewska E, Hryniewicz A, Moniuszko M, Kinter A, Smith KA, Franchini G. Contrasting effects of low-dose IL-2 on vaccine-boosted simian immunodeficiency virus (SIV)-specific CD4+ and CD8+ T cells in macaques chronically infected with SIVmac251. J Immunol. 2005 Feb 15;174(4):1913-21. — 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	Changing of viral load of SARS-CoV2	Copies of COVID-19 per ml	Day 1,3, 7, 12
Secondary	Changes in immunglobulin G COVID-19 antibody titer	Immunoglobulin G COVID-19 antibodies Immunglobulin G antibody titer	12 days
Secondary	Changes at the cytokine pattern		12 days
Secondary	Intensive Care Unit Admission	Proportion of patients with Intensive Care Unit Admission requirement	Day 7,12,28
Secondary	Length of hospital stay	Days of Hospitalization	Day 7, 12, 28
Secondary	Duration of mechanical ventilation	Days with mechanical ventilation	Day 7, 12, 28
Secondary	Clinical Status	Clinical status assessed according to the World Health Organization guideline	Day 7, 12, 28
Secondary	Mortality	Proportion of death patients at days	Day 7, 12, 28

External Links

•   12. Ethics of using convalescent whole blood and convalescent plasma during the Ebola epidemic. Interim guidance for ethics review committees, researchers, national health authorities and blood transfusion services. 2015 WHO/HIS/KER/GHE/15.1