NCT04345679

Brief 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
20

participants targeted

Target at P25-P50 for early_phase_1

Timeline
Completed

Started Apr 2020

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 11, 2020

Completed
3 days until next milestone

First Posted

Study publicly available on registry

April 14, 2020

Completed
Same day until next milestone

Study Start

First participant enrolled

April 14, 2020

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2021

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2021

Completed
Last Updated

February 25, 2021

Status Verified

February 1, 2021

Enrollment Period

1.1 years

First QC Date

April 11, 2020

Last Update Submit

February 23, 2021

Conditions

COVID 19

Keywords

COVID-19convalescent plasmaserum therapy

Outcome Measures

Primary Outcomes (1)

  • Changing of viral load of SARS-CoV2

    Copies of COVID-19 per ml

    Day 1,3, 7, 12

Secondary Outcomes (7)

  • Changes in immunglobulin G COVID-19 antibody titer

    12 days

  • Changes at the cytokine pattern

    12 days

  • Intensive Care Unit Admission

    Day 7,12,28

  • Length of hospital stay

    Day 7, 12, 28

  • Duration of mechanical ventilation

    Day 7, 12, 28

  • +2 more secondary outcomes

Study Arms (1)

Hospitalized patients with SARS CoV-2 infection

EXPERIMENTAL
Biological: anti-SARS-CoV-2 convalescent plasma

Interventions

anti-SARS-CoV-2 convalescent plasmaBIOLOGICAL

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

Hospitalized patients with SARS CoV-2 infection

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • age : \>18 and \<60 years
  • body weight : \>50 kg
  • confirmed previous SARS CoV-2 infection
  • negative SARS CoV-2 test result
  • written informed consent
  • neutralizing antibody titer min. 1 : 120

You may not qualify if:

  • 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.
  • age : \>18 years
  • admitted to hospital due to SARS CoV-2 infection
  • written informed consent
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Semmelweis University's Department of Pulmonology

Budapest, 1083, Hungary

RECRUITING

Related Publications (7)

  • 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.

    PMID: 32219428BACKGROUND

  • 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. doi: 10.1038/nm1201-1320.

    PMID: 11726972BACKGROUND

  • 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.

    PMID: 26618098BACKGROUND

  • 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.

    PMID: 31986264BACKGROUND

  • 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. No abstract available.

    PMID: 32192578BACKGROUND

  • Kardos D, Marschall B, Simon M, Hornyak I, Hinsenkamp A, Kuten O, Gyevnar Z, Erdelyi G, Bardos T, Paukovits TM, Magos K, Beres G, Szenthe K, Banati 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):824. doi: 10.3390/cells8080824.

    PMID: 31382623BACKGROUND

  • 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. doi: 10.4049/jimmunol.174.4.1913.

    PMID: 15699118BACKGROUND

Related Links

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Study Officials

  • Veronika Müller, MD, PhD

    Semmelweis University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Eszter Fodor, medical doctor

CONTACT

+36306640494eszter.fodor@orthosera.com

Zsombor Lacza, MD, PhD

CONTACT

+36305249554zsombor.lacza@orthosera.com

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 11, 2020

First Posted

April 14, 2020

Study Start

April 14, 2020

Primary Completion

June 1, 2021

Study Completion

September 1, 2021

Last Updated

February 25, 2021

Record last verified: 2021-02

Locations

HU(1)