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Convalescent Plasma for Treatment of COVID-19 Patients With Pneumonia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04374565
Recruitment Status : Recruiting
First Posted : May 5, 2020
Last Update Posted : May 8, 2020
Sponsor:
Information provided by (Responsible Party):
Jeffrey Sturek, MD, PhD, University of Virginia

Brief Summary:
This is a single arm phase II trial to assess efficacy and confirm safety of infusions of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms,with or without confirmed interstitial COVID-19 pneumonia by chest Xray or CT. A total of 29 eligible subjects will be enrolled to receive anti-SARS-CoV-2 plasma.Outcomes will be compared to hospitalized controls with confirmed COVID-19 disease through retrospective chart review.

Condition or disease Intervention/treatment Phase
Corona Virus Infection SARS-CoV 2 SARS Pneumonia Pneumonia Drug: High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma Phase 2

Detailed Description:

There are no proven treatments for coronavirus disease (COVID-19) and associated pneumonia caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Recent experience in China suggests that convalescent immune plasma(CIP)may be an effective treatment for COVID-19. In the pandemic situation where there are no vaccines for COVID-19, specific antibodies in convalescent plasma induced by infection may provide passive protective immunity. Passive antibody therapy was the first immunotherapy dating back to the 1890's for the treatment of infectious diseases before the development of antibiotics 1940's. Experience from prior outbreaks with other coronaviruses, such as SARS-CoV-1 shows that such convalescent plasma contains neutralizing antibodies to the relevant virus. In SARS-CoV-2, passive antibody therapy from CIP probably provided protection by viral neutralization. CIP was also used in the 2013 Ebola epidemic. A small non-randomized study in Sierra Leone revealed a significant increase in survival for who received CIP4. CIP administration is the only approach that provides immediate immunity to patients who have been exposed or who have active disease.

This approach is immediately available from individuals who have recovered, are viral free,and can donate immune plasma (IP) containing high titer neutralizing antibodies. Passive antibody therapy can be given to a patient recently exposed or a patient who is developing an infection with COVID-19 by obtaining plasma units from immune individuals by standard plasmapheresis using FDA-approved blood banking procedures, cross matching the unit(s) to the recipients and infusing the unit(s) using standard transfusion procedures for blood products. Based on the safety and long-term experience with plasma infusions, plasma exchanges, and other procedures involving plasma or plasma product, this protocol was designed as a phase II single arm trial that involves the administration of antibodies to a given agent to a susceptible individual for the purpose of preventing or treating an infectious disease due to that agent.

The only antibody formulation that is available for emergent use is that found in convalescent plasma. As more individuals contract COVID-19 and recover, the number of potential donors will increase.

The principle of passive antibody therapy is that it is more effective when used for prophylaxis than for treatment of disease. When used for therapy, antibody is most effective when administered shortly after the onset of symptoms. The reason for temporal variation in efficacy is not well understood but could reflect that passive antibody works by neutralizing the initial inoculum, which is likely to be much smaller than that of established disease. Alternatively, antibodies may dampen the early inflammatory response leaving the infected individual asymptomatic. For example, antibody therapy for pneumococcal pneumonia was most effective when given shortly after the onset of symptoms and was of no benefit if antibody therapy was delayed beyond the third day of disease. For passive antibody therapy to be effective, a sufficient amount of antibody must be infused. The antibody will circulate in the blood, reach tissues,and provide protection against infection. Depending on the type of antibody, amount, and composition, the half-life can vary from weeks to months. It is under these circumstances, the investigators plan to treat patients who are sick enough to be hospitalized before the onset of overwhelming disease involving a systemic inflammatory response, sepsis, and/or ARDS.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a single arm phase II trial to assess preliminary efficacy and confirm safety of infusions of antiSARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms with or without confirmed interstitial COVID-19 pneumonia by CXR or chest CT. A total of 29 eligible subjects will be enrolled to receive high titer anti-SARS-CoV-2 plasma. Participants will be compared to a historical control group via retrospective chart review.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of High-Titer Anti-SARS-CoV-2 (COVID19) Convalescent Plasma for Hospitalized Patients With Infection Due to COVID-19 to Decrease Complications: A Phase II Trial
Estimated Study Start Date : May 5, 2020
Estimated Primary Completion Date : April 5, 2021
Estimated Study Completion Date : April 5, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Experimental: Study participants
A total of 29 eligible subjects will be enrolled to receive high titer anti-SARS-CoV-2 plasma. Participants will be compared to a historical control group via retrospective chart review.
Drug: High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma
Pathogen reduced SARS-CoV-2 convalescent plasma (2 units; ~200 mL each for a total of 400mls) given preferably in one day, but allowable to be given over 2 days if clinical circumstances delay infusions in 1 day), with titer to be determined after the unit has been infused.




Primary Outcome Measures :
  1. Transfer to ICU [ Time Frame: Days 0 - 60 ]
    Will be done by comparing the admission rate to the ICU between patients who received convalescent plasma and a control group who did not enroll in the study, or receive another experimental therapy.

  2. 28 day mortality [ Time Frame: Days 0 - 60 ]
    Will be done by comparing the 28 day mortality rate between enrolled subjects and the control group.


Secondary Outcome Measures :
  1. Cumulative incidence of serious adverse events [ Time Frame: Days 0 - 60 ]
    Will be collected from time of enrollment until completion of the study. The adverse events will be evaluated by CTCAE V5.0 and MedDRA.

  2. Rates and duration of SARS-CoV-2 [ Time Frame: Days 0, 7, 14, and 21 ]
    Will be done by collecting respiratory tract swabs and testing for SARS-CoV-2 positivity.

  3. Serum of plasma antibody titer to SARS-CoV-2 [ Time Frame: Days 0, 7, 14, and 28 ]
    Serum or plasma will be collected and analyzed for SARS-CoV-2 antibody.

  4. Cellular and humoral immune response [ Time Frame: Days 0, 7, 14, 28 ]
    Blood will be collected and analyzed for cellular and humoral response.

  5. Supplemental oxygen free days [ Time Frame: Days 0-28 ]
    All days where a supplemental oxygen is needed will be recorded as a concomitant medication and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the supplemental oxygen free days.

  6. Ventilator free days [ Time Frame: Days 0 - 28 ]
    All days where a ventilator is needed will be recorded as a concomitant procedure and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ventilator free days.

  7. ICU free days [ Time Frame: Days 0 - 28 ]
    All days where the participant is admitted to the ICU will be recorded and subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ICU free days.

  8. Sequential organ failure assessment score [ Time Frame: days 0, 1, 4, 7, 14, 21, 28 ]
    The patient will be evaluated throughout their enrollment in the study. The score will be evaluated to see if the score improved or worsened throughout their admission.

  9. Need for vasopressors [ Time Frame: Days 0 - 60 ]
    Concomitant medications will be recorded throughout the patients participation in the study and vasopressors will be recorded, if they are needed.

  10. Need for renal replacement therapy [ Time Frame: Days 0 - 60 ]
    Renal function will be assessed throughout the patients participation in the study. If renal replacement therapy is needed, it will be captured as a concomitant procedure.

  11. Need for extracorporeal membrane oxygenation (ECMO) [ Time Frame: Days 0 - 60 ]
    Respiratory function will be assessed throughout the patients participation in the study. If ECMO is needed, it will be captured as a concomitant procedure.

  12. Hospital length of stay (LOS) [ Time Frame: Days 0-60 ]
    Will be calculated from the date the patient entered the hospital until they were discharged.

  13. ICU LOS [ Time Frame: days 0 - 60 ]
    Will be calculated from the date the patient entered the ICU until they were discharged from the ICU.

  14. Grade 3 or 4 Adverse Events (AEs) [ Time Frame: days 0 - 60 ]
    All adverse events will be recorded and evaluated by CTCAE v.5.0. All grade 3 and 4 AEs will be calculated to determine safety of convalescent plasma.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be 18 years of age or older
  • Patients hospitalized with COVID-19 respiratory symptoms within 72 hours of admission to a"floor" bed (non-ICU bed) and confirmation via SARS-CoV-2 RT-PCR testing.
  • Patient and/or surrogate is willing and able to provide written informed consent and comply with all protocol requirements.
  • Patients with hematologic malignancies or solid tumors are eligible.
  • Patients with autoimmune disorders are eligible.
  • Patients with immunodeficiency and organ or stem cell transplant recipients are eligible.
  • Patients who have received or are receiving hydroxychloroquine or chloroquine are eligible (but will be taken off the drug)
  • Prior use of IVIG is allowed but the investigator should consider the potential for a hypercoagulable state.

Exclusion Criteria:

  • Patients requiring mechanical ventilation or >6 liters per minute nasal cannula oxygen
  • Patients on other anti-COVID-19 trials being treated with tocilizumab (anti-IL-6 receptor), Siltuximab (anti-IL-2), Remdesivir, or other pharmacological trials that may be initiated hereafter.
  • A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the individual at a substantially increased risk of thrombosis (e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy).
  • Contraindication to transfusion or history of prior reactions to transfusion blood products.
  • Medical conditions for which receipt of 500-600 mL of intravenous fluid may be dangerous to the subject (e.g., decompensated congestive heart failure).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04374565


Contacts
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Contact: Kristen M Petros De Guex, MA 434) 924-5059 KMP6F@hscmail.mcc.virginia.edu
Contact: William B Harrington, MPH 434-409-5060 wh7fd@hscmail.mcc.virginia.edu

Locations
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United States, Virginia
University of Virginia Medical Center Recruiting
Charlottesville, Virginia, United States, 22903
Contact: Jeffrey Sturek, MD, PhD         
University of Virginia Not yet recruiting
Charlottesville, Virginia, United States, 22903
Contact: Kristen M Petros De Guex, MA    434-924-5059    KMP6F@hscmail.mcc.virginia.edu   
Principal Investigator: Jeffrey M. Sturek, MD, PhD         
Principal Investigator: Scott Heysell, MD         
Principal Investigator: Lawrence G. Lum, MD, DSc         
Sub-Investigator: Tania Thomas, MD, MPH         
Sub-Investigator: Chelsea Sheppard, MD         
Sub-Investigator: Alex Kadl, MD         
Sub-Investigator: Patrick Jackson, MD         
Sub-Investigator: Taison Bell, MD         
Sub-Investigator: Archana Thakur, PhD         
Sub-Investigator: Amy Mathers, MD         
Sub-Investigator: Melinda Poulter, PhD         
Sub-Investigator: James Gorham, MD         
Sub-Investigator: Karen Ballen, MD         
Sub-Investigator: Qin Liu, MD, PhD         
Sponsors and Collaborators
University of Virginia
Publications:
China puts 245 COVID-19 patients on convalescent plasma therapy. In: Huaxia, (ed): XinhuaNet, 2020.

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Responsible Party: Jeffrey Sturek, MD, PhD, Assistant Professor of Pulmonary and Critical Care Medicine, University of Virginia
ClinicalTrials.gov Identifier: NCT04374565    
Other Study ID Numbers: 200114
First Posted: May 5, 2020    Key Record Dates
Last Update Posted: May 8, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infection
Coronavirus Infections
Severe Acute Respiratory Syndrome
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Virus Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections