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

NCT04500067 | Completed Phase 3

• 1 other identifier: 2020-BV-BP
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 9

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

Conditions

Covid19; Pneumonia

Keywords

Pneumonia; COVID-19; SARS-CoV-2; IVIG; Immunoglobulin for Intravenous Administration; Bioven; Coronavirus

Outcome Measures

Primary Outcomes (5)

• Period duration (in days) to clinical improvement

  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)

  From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days

• O2 saturation (SPO2 percentage), with self-breathing

  The target level of SPO2 percentage - 95% and above with self-breathing, is used as one of the clinical improvement criteria

  From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days

• Respiratory movements rate (amount per minute), with self-breathing

  The target level of respiratory movements - 28 per minute or less with self-breathing, is used as one of the clinical improvement criteria

  From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days

• Body temperature without antipyretics use

  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.

  From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days

• Lymphocyte count

  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)

  From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days

Secondary Outcomes (15)

• Time from the onset of the disease to discharge, in days

  28 days

• Duration of the need for ventilatory support, in days

  28 days

• Duration of the need for intensive care, in days

  28 days

• Duration of need for oxygenation in days (SPO2 ≤ 93% with self-breathing)

  28 days

• The C-reactive protein (CRP) level

  Day 0 (screening), day 5, day 14, day 28

Other Outcomes (2)

• Frequency of side effects

  28 days

• Frequency of serious side effects

  28 days

Study Arms (2)

Study Group (IVIG)

EXPERIMENTAL

Patients receive IVIG (trade name - Bioven) with base therapy

Drug: IVIG

Control group

NO INTERVENTION

Patients receive base therapy only

Interventions

IVIG DRUG

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.

Also known as: Human normal immunoglobulin for intravenous administration, Bioven

Study Group (IVIG)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biopharma Plasma LLC: lead
• Lviv National Medical University: collaborator
• Vinnitsa National Medical University: collaborator

Study Sites (9)

Site 08 - "Central City Clinical Hospital of Ivano-Frankivsk City Council"

Ivano-Frankivsk, Ivano-Frankivs'k Region, 76018, Ukraine

Location

Site 02 - "Bila Tserkva City Hospital №3"

Bila Tserkva, Kyiv Oblast, 09112, Ukraine

Location

Site 03 - "Lviv Regional Infectious Diseases Clinical Hospital"

Lviv, Lviv Oblast, 79010, Ukraine

Location

Site 04 - "City Clinical Infectious Diseases Hospital", Odesa

Odesa, Odesa Oblast, 65021, Ukraine

Location

Site 07 - "Ternopil City Municipal Ambulance Hospital"

Ternopil, Ternopil Oblast, 46006, Ukraine

Location

Site 06 - "Vinnytsia City Clinical Hospital №1"

Vinnitsia, Vinnitsia Region, 21021, Ukraine

Location

Site 09 - "Volyn Regional Clinical Hospital"

Lutsk, Volyn Oblast, 43000, Ukraine

Location

Site 01 - "Kyiv City Clinical Hospital №17"

Kyiv, 03110, Ukraine

Location

Site 05 - "Kyiv City Clinical Hospital №4"

Kyiv, 03110, Ukraine

Location

MeSH Terms

Conditions

COVID-19; Pneumonia; Coronavirus Infections

Interventions

Immunoglobulins, Intravenous; gamma-Globulins; Administration, Intravenous

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Drug Administration Routes; Drug Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 15, 2020
• First Posted: August 5, 2020
• Study Start: May 7, 2020
• Primary Completion: September 15, 2020
• Study Completion: September 15, 2020
• Last Updated: October 14, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: After trial result publication 3 months later
• Access Criteria: For specialists in medicine, pharmacy, scientists

Locations

UA (9)