Clinical trial NCT04642014: Application of Convalescent Plasma in the Treatment of SARS CoV-2 Disease (COVID-19) With Evaluation of Therapy Effectiveness
Official title: A Multi-centre, 18-months, Single-group Study of Application of Convalescent Plasma in the Treatment of SARS CoV-2 Disease (COVID-19) With Metabolomic and Laboratory Evaluation of Plasma Therapy Effectiveness
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: COVID-19 Convalescent Plasma Treatment
Lead sponsor: Wroclaw Medical University
Sponsor class: OTHER
Collaborators: name: Medical Research Agency, Poland
First posted: 2020-11-24
Enrollment: 396
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The study is going to recruit 300 convalescent plasma donors and 200 recipients
Primary purpose: TREATMENT

Brief summary: A Multi-centre, 18-months, Single-group Study of Application of Convalescent Plasma in the Treatment of SARS CoV-2 Disease (COVID-19) With Metabolomic and Laboratory Evaluation of Plasma Therapy Effectiveness.

Detailed description: The trial is designed as multi-centre, non-randomized, single-group with a primary endpoint of death of convalescent plasma recipient in twenty eight days. We are planning to recruit 300 donor patients who recovered from COVID-19 and who offer to take part in an experiment based on the informed consent form. The recovery criteria involve body temperature normalization for more than 3 days, resolution of respiratory tract symptoms, and two consecutively negative results of SARS-CoV-2 RT-PCR assay test. The donor's blood will be collected after four weeks post-onset of illness. 600 ml ABO-compatible plasma sample will be harvested during apheresis from each donor and each sample will be divided and stored as 200 mL aliquots. The plasma recipients are adult patients diagnosed with COVID-19 according to the WHO Interim Guidance with confirmation by real-time RT-PCR assay The inclusion criteria to receive plasma assume to meet at least one of following : respiratory distress with tachypnoe ≥30 breaths per minute, oxygen level less than 94% in resting-state, partial pressure of oxygen (PO2) ≤ 80 mmHg. Patients who meet the criteria receive one dose (200 mL) of ABO compatible inactivated convalescent plasma with a confirmed neutralization activity. The recipient are going to undergo detailed clinical evaluation along with the assessment of biochemical parameters, complete blood count and inflammation indicators. The study involves a comprehensive assessment of the serological response of patients with different course of SARS-Cov-2 infection, as well as an analysis of the impact of the level of antibodies in the donor's plasma on the clinical response in patients with COVID-19. In addition, a comprehensive metabolomic analysis of donor and recipient blood was planned to identify prognostic and predictive factors. The endpoints include the safety of convalescents plasma transfusion, as well as the improvement of clinical symptoms and laboratory parameters.

Eligibility criteria: Inclusion Criteria:

Donors:

1. Age \>18 and \<65 years
2. Confirmed previous SARS CoV-2 infection
3. Signed informed consent to participate in this clinical trial, to donate plasma and to store the specimen for future testing.
4. At least 28 days from the end of isolation or resolution of symptoms of infection
5. Male donors, or female donors who have not been pregnant, or female donors who have been pregnant tested negative for HLA antibodies
6. Individuals who meet all regular voluntary donor eligibility requirements

Recipiants:

1. Signed informed consent to participate in this clinical trial.
2. Confirmed previous SARS CoV-2 infection
3. Respiratory distress with tachypnoe ≥30 breaths per minute,
4. Oxygen level less than 94% in resting-state,
5. Partial pressure of oxygen (PO2) ≤ 80 mmHg

Exclusion Criteria:

Donors:

1. Age : \<18 or \>65 years
2. Female subjects who are pregnant
3. HIV1,2 hepatitis B,C or syphilis infection
4. Donors ineligible for regular voluntary blood donation

Recipiants:

1. No informed consent to participate in the study
2. Patients with a history of plasma hypersensitivity, including anaphylactic shock in previous transfusions, allergic reactions to citrate or primary IgA deficiency
3. Patients with symptoms of severe multi-organ failure
4. Patients with known allergic reactions to chemical compounds used or generated in the procedure of inactivation of pathogens
5. Patients with active thrombosis

Primary outcomes:
measure: Death, for any reason
timeFrame: 28 days after transfusion
Secondary outcomes:
measure: For patients with respiratory support, the time to take one's own breath (extubation)
timeFrame: 28 days after transfusion
measure: Stay in the intensive care unit (ICU)
timeFrame: 28 days after transfusion
measure: Time to disconnect CPAP respiratory support
timeFrame: 28 days after transfusion
measure: Time to elimination of SARS-Cov-2 (RT-PCR)
timeFrame: 28 days after transfusion
measure: Time to serological response (anti-SARS-COv-2 antibodies)
timeFrame: 3, 7, 28 days after transfusion
Other outcomes:
Locations:
city: Wroclaw
country: Poland
facility: Wroclaw Medical University
state: Dolnośląskie
Study officials:
References:
citation: Rajendran K, Krishnasamy N, Rangarajan J, Rathinam J, Natarajan M, Ramachandran A. Convalescent plasma transfusion for the treatment of COVID-19: Systematic review. J Med Virol. 2020 Sep;92(9):1475-1483. doi: 10.1002/jmv.25961. Epub 2020 May 12.
citation: Li L, Zhang W, Hu Y, Tong X, Zheng S, Yang J, Kong Y, Ren L, Wei Q, Mei H, Hu C, Tao C, Yang R, Wang J, Yu Y, Guo Y, Wu X, Xu Z, Zeng L, Xiong N, Chen L, Wang J, Man N, Liu Y, Xu H, Deng E, Zhang X, Li C, Wang C, Su S, Zhang L, Wang J, Wu Y, Liu Z. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial. JAMA. 2020 Aug 4;324(5):460-470. doi: 10.1001/jama.2020.10044.
citation: Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, Zhou M, Chen L, Meng S, Hu Y, Peng C, Yuan M, Huang J, Wang Z, Yu J, Gao X, Wang D, Yu X, Li L, Zhang J, Wu X, Li B, Xu Y, Chen W, Peng Y, Hu Y, Lin L, Liu X, Huang S, Zhou Z, Zhang L, Wang Y, Zhang Z, Deng K, Xia Z, Gong Q, Zhang W, Zheng X, Liu Y, Yang H, Zhou D, Yu D, Hou J, Shi Z, Chen S, Chen Z, Zhang X, Yang X. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. 2020 Apr 28;117(17):9490-9496. doi: 10.1073/pnas.2004168117. Epub 2020 Apr 6.
citation: Ye M, Fu D, Ren Y, Wang F, Wang D, Zhang F, Xia X, Lv T. Treatment with convalescent plasma for COVID-19 patients in Wuhan, China. J Med Virol. 2020 Oct;92(10):1890-1901. doi: 10.1002/jmv.25882. Epub 2020 Jun 29.
citation: Yigenoglu TN, Hacibekiroglu T, Berber I, Dal MS, Basturk A, Namdaroglu S, Korkmaz S, Ulas T, Dal T, Erkurt MA, Turgut B, Altuntas F. Convalescent plasma therapy in patients with COVID-19. J Clin Apher. 2020 Aug;35(4):367-373. doi: 10.1002/jca.21806. Epub 2020 Jul 9.
citation: Joyner MJ, Wright RS, Fairweather D, Senefeld JW, Bruno KA, Klassen SA, Carter RE, Klompas AM, Wiggins CC, Shepherd JR, Rea RF, Whelan ER, Clayburn AJ, Spiegel MR, Johnson PW, Lesser ER, Baker SE, Larson KF, Ripoll JG, Andersen KJ, Hodge DO, Kunze KL, Buras MR, Vogt MN, Herasevich V, Dennis JJ, Regimbal RJ, Bauer PR, Blair JE, Van Buskirk CM, Winters JL, Stubbs JR, Paneth NS, Verdun NC, Marks P, Casadevall A. Early safety indicators of COVID-19 convalescent plasma in 5000 patients. J Clin Invest. 2020 Sep 1;130(9):4791-4797. doi: 10.1172/JCI140200.