Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy of Convalescent Plasma Therapy in Severely Sick COVID-19 Patients

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04346446
Recruitment Status : Completed
First Posted : April 15, 2020
Last Update Posted : June 12, 2020
Sponsor:
Information provided by (Responsible Party):
Institute of Liver and Biliary Sciences, India

Tracking Information
First Submitted Date  ICMJE April 14, 2020
First Posted Date  ICMJE April 15, 2020
Last Update Posted Date June 12, 2020
Actual Study Start Date  ICMJE April 20, 2020
Actual Primary Completion Date May 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 14, 2020)
Proportion of patients remaining free of mechanical ventilation in both groups [ Time Frame: Day 7 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2020)
  • Mortality in both groups [ Time Frame: Day 28 ]
  • Improvement in Pa02/Fi02 ratio in both groups [ Time Frame: Day 2 ]
  • Improvement in Pa02/Fi02 ratio in both groups [ Time Frame: Day 7 ]
  • Improvement in SOFA score in both groups [ Time Frame: Day 2 ]
  • Improvement in SOFA score in both groups [ Time Frame: Day 7 ]
  • Duration of hospital Stay in both group. [ Time Frame: Day 28 ]
  • Duration of Intensive Care Unit stay in both groups. [ Time Frame: Day 28 ]
  • Requirements of Vasopressor in both groups. [ Time Frame: Day 28 ]
  • Days free of dialysis in both groups. [ Time Frame: Day 28 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Convalescent Plasma Therapy in Severely Sick COVID-19 Patients
Official Title  ICMJE Efficacy of Convalescent Plasma Therapy in Severely Sick COVID-19 Patients: A Pilot Randomized Controlled Trial
Brief Summary Currently, no effective treatments are available for the COVID-19 pandemic, which is related to more than 70,000 deaths all over the world. Scientists and Researchers are working on many aspects of treatment options for the development of vaccination and medication to combat this life-threatening problem. Convalescent plasma from recovered COVID-19 patients contains antibodies against COVID-19 which may be beneficial to severely sick COVID019 infected patients. We have planned a randomized controlled trial to assess the efficacy of this therapy in COVID-19 infected sick patients. We will collect up to 500 ml Convalescent Plasma from the COVID-19 infected recovered patient after 14 days of clinical and radiological recovery with two consecutive COVID-19 negative tests by PCR. We will further test the sample from the collected plasma for COVID-19 specific antibodies and their titer. This plasma will be frozen and sent to the treating center (MAMC). 200-600 ml of convalescent plasma will be transfused to patients who fit the eligibility criteria and are randomized to the convalescent plasma group. This will be done in severely sick patients. Data will be collected for the benefit and adverse events related to convalescent plasma transfusion.
Detailed Description

For Donors:

Microtiter plates will be coated overnight at 4°C with 4 μg/mL recombinant SARS-CoV-2 RBD (receptor binding domain) proteins (50 μL per well). The plates will be washed 3 times with phosphate-buffered saline (PBS) containing 0.1% vol/vol Tween-20(PBST) and blocked with blocking solution (PBS containing 2% wt/vol nonfat dry milk) for 2 hours at 37 °C. The plates will be then washed with PBST. The serum samples will be diluted to 200-fold into PBS as initial concentration, and serial 3-fold dilutions of serum will be added to the wells and incubated at 37 °C for 60 minutes. After 3 washes, 100 μL of horseradish peroxidase-conjugated goat anti-human IgG (for IgG antibody titer detection)and IgM (for IgM antibody titer detection) antibodies solution will be added to each plate, respectively, and incubated at 37 °C for 60 minutes. After 5 washes, 100 μL of tetramethylbenzidine substrate will be added at room temperature in the dark. After 15 minutes, the reaction will be stopped with a2MH2SO4 solution (sulfuric acid). The absorbance will be measured at 450nm. All samples will be run in triplicate. The IgG titers will be determined by endpoint dilution.

Serum Neutralization Assay Vero cells (104) will be seeded 24 hours before the infection in a 96-well plate. On the day of infection, the cells will be washed twice. Serum samples from patients will be incubated at 56 °C for 30 minutes and then diluted 2-fold in cell culture medium (modified eagle medium). Aliquots (40 μL) of diluted serum samples (from2-fold to 2056-fold) will be added to 50 μL of cell culture medium containing 50 times the tissue culture infective dose (TCID50) of the virus strain on a 96-well plate and incubated at 37 °C for 2 hours in CO2 5% vol/vol. Virus antibody mix will be added to cells in 96-well plates and plates will be incubated at 37 °C with a microscopic examination for cytopathic effect after 5-day incubation. The highest dilution of serum that showed inhibition activity of SARS-CoV-2 will be recorded as the neutralizing antibody titer. Assays will be performed in triplicate with negative control samples from healthy volunteers.

For recipients:

The serum of each recipient will be obtained and enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody titers will be tested one day prior to the convalescent plasma transfusion. Changes of Receptor Binding Domain-Specific IgG titre and neutralizing antibody titers before and after convalescent plasma transfusion in patients will be obtained on day 0, day 1, day 3 and day 7. if possible.

All included patients would be randomized to receive either standard medical therapy (supportive therapy) with random donor plasma versus convalescent plasma and standard medical therapy Clinical information of all enrolled patients including symptoms at presentation, time to presentation to the hospital and development of pulmonary symptoms would be recorded. The details of comorbid diseases as measured by the Charlson index of comorbidity and Acute Physiology and Chronic Health Evaluation II (APACHE II). Details of cross-sectional imaging, chest-x-ray, bacterial or fungal co-infections and details of antibiotic treatment would be recorded. Development of complications including acute kidney injury, acute coronary syndrome, myocarditis, acute respiratory distress syndrome, and nosocomial infection will be recorded. The use of high-flow oxygen, non-invasive and invasive ventilation will follow standard guidelines and will be recorded. The details of antiviral treatment including oral oseltamivir, hydroxychloroquine, and use of intravenous steroids will be recorded for all enrolled patients.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE COVID
Intervention  ICMJE
  • Drug: Convalescent Plasma Transfusion
    Convalescent Plasma Transfusion
  • Other: Supportive Care
    Supportive Care
  • Drug: Random Donor Plasma
    Random Donor Plasma will be transfuse from 200 to 600 mL according to the patient requirement
Study Arms  ICMJE
  • Experimental: Convalescent Plasma+Supportive Care
    Convalescent Plasma+Supportive Care Convalescent plasma from recovered COVID-19 patients will be transfused to severely sick COVID-19 infected patients
    Interventions:
    • Drug: Convalescent Plasma Transfusion
    • Other: Supportive Care
  • Active Comparator: Random Donor Plasma+Supportive Care
    Random Donor Plasma+Supportive Care
    Interventions:
    • Other: Supportive Care
    • Drug: Random Donor Plasma
Publications * Piechotta V, Iannizzi C, Chai KL, Valk SJ, Kimber C, Dorando E, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Estcourt LJ, Skoetz N. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 May 20;5:CD013600. doi: 10.1002/14651858.CD013600.pub4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 4, 2020)
29
Original Estimated Enrollment  ICMJE
 (submitted: April 14, 2020)
20
Actual Study Completion Date  ICMJE May 30, 2020
Actual Primary Completion Date May 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

-

Recipient:

Severe COVID -19 infections defined as WHO Interim Guidance and the Guideline of Diagnosis and Treatment of COVID-19 of National Health Commission of China (version 5.0) with confirmation by real-time RT-PCR assay with severe disease i.e. meeting any 2 of the following criteria-

  1. Respiratory distress, RR ≥30 beats/min
  2. Oxygen saturation level less than 93% in resting state
  3. Partial pressure of oxygen (PaO2)/oxygen concentration (FiO2) ≤ 300 mmHg.
  4. Lung infiltrates > 50% within 24 to 48 hours
  5. Very sick (on ventilator) and patients with co-morbidities such as patients with known co-morbid diseases (COPD, CAD, CLD, CKD, cardiopulmonary disease-structural or valvular heart disease)
  6. Patient presenting with multi organ failure or requiring mechanical ventilation.

Donor:

  • Known case of recovered COVID-19 Infection, and
  • Complete resolution of symptoms at least 28 days prior to donation or Complete resolution of symptoms at least 14 days prior to donation and negative results for COVID-19 either from one or more nasopharyngeal swab specimens or by a molecular diagnostic test from the blood, And Negative RT-PCR for COVID-19 on two sequential paired nasopharyngeal and throat specimens > 24 hrs apart (WHO-CDC guideline).
  • Donor Plasma after 2 negative tests and 2 weeks of remaining asymptomatic, without antibody titre & presence of IgG/IgM antibodies to COVID-19 by serological as per manufacturers instructions. Donors negative for these will be deferred).
  • Fulfill all criteria of donor eligibility for donor Plasmapheresis under the Drugs & Cosmetics Act and Rules 1945, amended 11.03.2020.

Exclusion Criteria:

- Recipient

  • Patients with age less than 18 years.
  • Pregnancy
  • Individual with HIV and Hepatitis
  • Morbid Obesity BMI>35 kg/m2
  • Extremely moribund patients with an expected life expectancy of less than 24 hours.
  • Failure to give informed consent from the patient or family members.
  • Hemodynamic instability requiring vasopressors.
  • Previous allergic history to plasma.

Donor:

  • Donors age < 18 & ≥60 years old
  • Do not fulfil all criteria of donor eligibility for donor Plasmapheresis under the Drugs & Cosmetics Act and Rules 1945, amended 11.03.2020.
  • Females who have been pregnant and previously transfused donors (to prevent TRALI).
  • Donors who have taken steroids during treatment for COVID-19.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE India
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04346446
Other Study ID Numbers  ICMJE ILBS-COVID-02
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party Institute of Liver and Biliary Sciences, India
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Institute of Liver and Biliary Sciences, India
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Institute of Liver and Biliary Sciences, India
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP