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Intravenous Immunoglobulin (IVIG, Bioven) Efficacy Assess for COVID-19 / SARS-CoV-2 Severe Pneumonia Complex Treatment

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ClinicalTrials.gov Identifier: NCT04500067
Recruitment Status : Completed
First Posted : August 5, 2020
Last Update Posted : October 14, 2020
Sponsor:
Collaborators:
Lviv National Medical University
Vinnitsa National Medical University
Information provided by (Responsible Party):
Biopharma Plasma LLC

Brief Summary:

Pneumonia caused by coronavirus infection COVID-19 is characterized by a combination of several dangerous factors that consistently worsen the patient's condition: viral lung damage early in the disease; a sharp increase in inflammation on the background of an unbalanced immune response ("cytokine storm"); joining a bacterial infection.

The condition of patients deteriorates significantly mostly at cytokine storm development. The damaging of a large volume of lung tissue leads to develops of respiratory failure, respiratory distress syndrome, or shock. Ventilatory support becomes ineffective and patients die.

There are reports of the effectiveness of Human Normal Immunoglobulin for Intravenous Administration (IVIG) high doses when used as part of complex therapy in patients with pneumonia caused by coronavirus COVID-19. In particular, IVIG has a positive effect on survival rates, overall disease course, duration of stay in the intensive care unit, and ventilatory support duration.

The probable mechanism of action of high-dose IVIG therapy is considered to be a regulatory effect on the immune system. Similar is the known and confirmed effectiveness of IVIG for autoimmune diseases (Kavasaky disease, Guillain Barre syndrome, Chronic inflammatory demyelinating polyradiculoneuropathy, Multifocal motor neuropathy).

This trial to assesses the Efficacy of IVIG (medication trade name - Bioven, manufactured by Biopharma Plasma LLC) in the High Immunomodulatory Dose in Complex Treatment of Severe Pneumonia Caused by COVID-19 / SARS-CoV-2


Condition or disease Intervention/treatment Phase
Covid19 Pneumonia Drug: IVIG Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Open-label multicenter randomized controlled in parallel groups.

Patients undergoing screening are randomized into groups in equal proportions:

  • Study Group (receive IVIG Bioven with base therapy).
  • Control group (receive base therapy only)

At the stage of Data Analysis to ensure comparability of data and homogeneity of the sample, the possibility of additional comparison of groups based on the actually prescribed base therapy and other identified covariates is provided.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Multicenter Randomized Trial to Evaluate the Efficacy of Bioven, Manufactured by Biopharma Plasma, LLC, in Complex Therapy of Patients With Pneumonia Induced by COVID-19 / SARS-CoV-2
Actual Study Start Date : May 7, 2020
Actual Primary Completion Date : September 15, 2020
Actual Study Completion Date : September 15, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
Experimental: Study Group (IVIG)
Patients receive IVIG (trade name - Bioven) with base therapy
Drug: IVIG
Patients in the study group receive the drug Bioven, 10% solution for infusions produced by LLC Biopharma Plasma 0,8-1,0 g/kg once a day for 2 days (total course dose - 1.6-2.0 g/kg) as well as base treatment recommended by the protocol of COVID-19 coronavirus infection treatment depending on the severity of their condition according to the prescription sheet.
Other Names:
  • Human normal immunoglobulin for intravenous administration
  • Bioven

No Intervention: Control group
Patients receive base therapy only



Primary Outcome Measures :
  1. Period duration (in days) to clinical improvement [ Time Frame: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days ]
    Number of days post-onset of severe pneumonia to the moment of normalization at least two from following primary outcomes: O2 saturation with self-breathing, respiratory movements rate with self-breathing, body temperature without antipyretics use, lymphocyte count (targeted levels set in the description each of these primary outcomes)

  2. O2 saturation (SPO2 percentage), with self-breathing [ Time Frame: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days ]
    The target level of SPO2 percentage - 95% and above with self-breathing, is used as one of the clinical improvement criteria

  3. Respiratory movements rate (amount per minute), with self-breathing [ Time Frame: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days ]
    The target level of respiratory movements - 28 per minute or less with self-breathing, is used as one of the clinical improvement criteria

  4. Body temperature without antipyretics use [ Time Frame: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days ]
    Measured in degrees Celsius. Fever absence (body temperature no more 37 degrees Celsius) during at least 24 hours without antipyretics, is used as one of the clinical improvement criteria.

  5. Lymphocyte count [ Time Frame: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days ]
    The target level 1000 cells / mm3 and above is used as one of the clinical improvement criteria (applicable for patients with lymphocytes count lower 1000 cells / mm3 at screening moment)


Secondary Outcome Measures :
  1. Time from the onset of the disease to discharge, in days [ Time Frame: 28 days ]
    Period duration (in days)

  2. Duration of the need for ventilatory support, in days [ Time Frame: 28 days ]
    Number of days with ventilatory support

  3. Duration of the need for intensive care, in days [ Time Frame: 28 days ]
    Number of days in the intensive care unit

  4. Duration of need for oxygenation in days (SPO2 ≤ 93% with self-breathing) [ Time Frame: 28 days ]
    Number of days with necessery of oxygenation support

  5. The C-reactive protein (CRP) level [ Time Frame: Day 0 (screening), day 5, day 14, day 28 ]
    Measuring the analyte concentration in plasma (mg/L)

  6. The tumor necrozis factor alpha (TNF-α) level [ Time Frame: Day 0 (screening), day 5, day 14, day 28 ]
    Measuring the analyte concentration in plasma (pg/mL)

  7. The interleukin-1β (IL-1β) level [ Time Frame: Day 0 (screening), day 5, day 14, day 28 ]
    Measuring the analyte concentration in plasma (pg/mL)

  8. The interleukin-6 (IL-6) level [ Time Frame: Day 0 (screening), day 5, day 14, day 28 ]
    Measuring the analyte concentration in plasma (pg/mL)

  9. The D-dimer level [ Time Frame: Day 0 (screening), day 5, day 14, day 28 ]
    Measuring the analyte concentration in plasma (µg FEU/mL)

  10. The Complement (C3 component) level [ Time Frame: Day 0 (screening), day 5, day 14, day 28 ]
    Measuring the analyte concentration in plasma (g/L)

  11. The Circulating immune complexes level [ Time Frame: Day 0 (screening), day 5, day 14, day 28 ]
    Measuring the analyte concentration in plasma (U/mL)

  12. The ferritin level [ Time Frame: Day 0 (screening), day 5, day 14, day 28 ]
    Analyte concentration in plasma (ng/mL)

  13. The procalcitonin level [ Time Frame: Day 0 (screening), day 5, day 14, day 28 ]
    Analyte concentration in plasma (ng/mL)

  14. IgG subtypes [ Time Frame: Day 0 (screening), day 5, day 14, day 28 ]
    The IgG-subtypes (IgG1-IgG4) concentration in plasma (mg/dL)

  15. Survival assessment for a 28-day follow-up period since the onset of severe pneumonia [ Time Frame: 28 days ]
    Survivealance estimation


Other Outcome Measures:
  1. Frequency of side effects [ Time Frame: 28 days ]
    Number of participants with adverse reactions related by investigational drug as assessed by CTCАЕ v 4.0

  2. Frequency of serious side effects [ Time Frame: 28 days ]
    Number of participants with serious adverse reactions related by investigational drug as assessed by CTCАЕ v 4.0



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:

  • Men and women 18 years of age and older;
  • COVID-19 documentary confirmed by PCR lab test;
  • severe pneumonia caused by COVID-19 according to the criteria below:

    • - fever or suspicion of respiratory infection;
    • - the number of respiratory movements 30 per 1 min and above;
    • - severe respiratory failure or SpO2 <90% with spontaneous breathing indoors;
    • - the presence of foci of inflammation in the lungs according to the results of computed tomography, which is documented.
    • or if any of the conditions listed below have developed on the background of previously diagnosed coronavirus pneumonia:

      • - severe respiratory failure required mechanical ventilation (ALV);
      • - acute respiratory distress syndrome according to WHO diagnostic criteria (development within one week after the manifestation of disease clinical symptoms or emergence of new ones or deterioration of respiratory syndromes. Chest visualization (lung X-ray, CT or ultrasound); bilateral opacities not fully explaining the gravity of condition or lung collapse or nodules);
      • - sepsis according to WHO diagnostic criteria (life-threatening organ dysfunction caused by disturbance of host reaction to suspected or proven infection. The features of organ dysfunction include the following: mental change, labored or shallow breathing, low oxygenation, oliguria or anuria, rapid heart palpitation, weak pulse, cold extremities or low blood pressure, skin blotching or lab-proven coagulopathy, thrombocytopenia, acidosis, high level of lactic acid or hyperbilirubinemia);
      • - endotoxic shock according to WHO diagnostic criteria (persisting hypotension despite extensive resuscitation requiring vasoconstrictors for maintaining mean arterial pressure ≥ 65 mmHg and serum lactate level > 2 mmol/l);
  • the signed patient's informed consent to participation in the trial;
  • the negative pregnancy test (for female patients of reproductive age), readiness to use reliable contraception methods during the whole duration of the trial.
  • the ability, according to the researcher, to follow all requirements of the research protocol.
  • this study allows you to take into account the results of examinations related to the disease, conducted within 10 days before signing the Informed Consent. Such data are transferred from the primary documentation to the CRF.

Exclusion Criteria:

  • known intolerance to plasma or immunoglobulin drugs;
  • drug allergy or hypersensitization to immunoglobulin drugs;
  • any known counter-indication to immunoglobulin drugs according to the instruction for medical application of the tested drug;
  • pneumonia not associated with COVID-19 infection;
  • pregnancy, lactation period;
  • any clinically significant impairment of liver function (elevation of serum transaminase levels more than 3 times the upper limit of normal);
  • serum creatinine levels more than 2 times the upper limit of normal for a given age and gender;
  • established diagnosis of primary immunodeficiency;
  • verified HIV-infection;
  • immune diseases (blood immune diseases, rheumatic diseases, nephritis, etc.)
  • severe cardiovascular failure (Stage III);
  • mental illness in anamnesis;
  • the need for prescribing medicines or procedures that are incompatible with the administration of the drug within the scope of this study: monoclonal antybodies;
  • known drug addiction;
  • participation in any other clinical trial presently or within the last 30 days.

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): NCT04500067


Locations
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Ukraine
Site 08 - "Central City Clinical Hospital of Ivano-Frankivsk City Council"
Ivano-Frankivs'k, Ivano-Frankivs'k Region, Ukraine, 76018
Site 02 - "Bila Tserkva City Hospital №3"
Bila Tserkva, Kyiv Region, Ukraine, 09112
Site 03 - "Lviv Regional Infectious Diseases Clinical Hospital"
Lviv, Lviv Region, Ukraine, 79010
Site 04 - "City Clinical Infectious Diseases Hospital", Odesa
Odesa, Odesa Region, Ukraine, 65021
Site 07 - "Ternopil City Municipal Ambulance Hospital"
Ternopil', Ternopil' Region, Ukraine, 46006
Site 06 - "Vinnytsia City Clinical Hospital №1"
Vinnitsia, Vinnitsia Region, Ukraine, 21021
Site 09 - "Volyn Regional Clinical Hospital"
Luts'k, Volyn Region, Ukraine, 43000
Site 01 - "Kyiv City Clinical Hospital №17"
Kyiv, Ukraine, 03110
Site 05 - "Kyiv City Clinical Hospital №4"
Kyiv, Ukraine, 03110
Sponsors and Collaborators
Biopharma Plasma LLC
Lviv National Medical University
Vinnitsa National Medical University
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Responsible Party: Biopharma Plasma LLC
ClinicalTrials.gov Identifier: NCT04500067    
Other Study ID Numbers: 2020-BV-BP
First Posted: August 5, 2020    Key Record Dates
Last Update Posted: October 14, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: After completion of the trial, results will be published. Access to parts CSR planned after the release of scientific publications
Supporting Materials: Clinical Study Report (CSR)
Time Frame: After trial result publication 3 months later
Access Criteria: For specialists in medicine, pharmacy, scientists

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Biopharma Plasma LLC:
Pneumonia
COVID-19
SARS-CoV-2
IVIG
Immunoglobulin for Intravenous Administration
Bioven
Coronavirus
Additional relevant MeSH terms:
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Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs