Infections, Coronavirus
Conditions
Brief summary
The study is designed as an open observational non-comparative study of Polyoxidonium®, lyophilizate for solution for injections and topical application, 12 mg in hospitalized patients with coronavirus disease (COVID-19).
Detailed description
The study was planned as an observation of Polyoxidonium® administered in addition to Russian Ministry of Healthcare (MoH) guidance for standard COVID-19 treatment. Regimens have no limitations to the use of concomitant therapy. The aim of the study is to observe the safety and efficacy of Polyoxidonium®, lyophilizate for solution for injections, 12 mg in addition to complex treatment of hospitalized patients with COVID-19.
Interventions
DRUGPolyoxidonium
Polyoxidonium (azoximer bromide) is administered in the dose of 12 mg (contents of 2 vials) once daily intravenously (IV) for 3 days, then every other day intramuscularly (IM) on days 5-17 (the total treatment course is 10 injections)
Sponsors
NPO Petrovax
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Inclusion criteria
1. The hospitalized patient was administered Polyoxidonium, according to the instruction for medical usage in complex with Russian MoH guidance for treatment of COVID-19. 2. Verified coronavirus disease COVID-19, and at least one of the following: * severe disease: mechanical ventilation or oxygen supply required with blood oxygen saturation (SpO2) ≤ 94% on room air or tachypnea, respiratory rate ≥ 24 breaths per minute, * mild-moderate disease: SpO2 \> 94% on room air or respiratory rate \< 24 breaths per minute. 3. The patient signed an Informed Consent form for participation in this study. 4. The patient can understand all protocol requirements, perform the study procedures, and agree to all limitations specified in the protocol. 5. Male and female patients from 18 years of age. 6. Confirmed diagnosis of coronavirus disease (COVID-19): laboratory-confirmed Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR), or other commercial or public health assay in any specimen prior to inclusion.
Exclusion criteria
1. Pregnancy or breastfeeding. 2. Pathological condition that the study doctor considers significant enough to prevent enrolment of this patient. 3. Participation in any clinical study within 30 days before the Informed Consent form provided. 4. Hypersensitivity and/or intolerability to any ingredient of the investigational product. 5. Acute or chronic renal failure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Status of the Patient (According to 7-point Ordinal Scale) | Day 1 (Baseline), Day 15 | Subject clinical status using the 7-point Ordinal Scale, specified as the primary endpoint in the WHO Master Protocol on day 15 as compared to baseline (1 - Not hospitalized, no limitations on activities; 2 - Not hospitalized, limitation on activities; 3 - Hospitalized, not requiring supplemental oxygen; 4 - Hospitalized, requiring supplemental oxygen; 5 - Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6 - Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation; 7 - Death). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Improvement in Clinical Status of the Patient (According to Ordinal Scale) by 1 Point for Each OS Score | Days 1 - 29. | Ordinal scale (OS) score status, time to improvement by 1 point for each OS score. Subject clinical status using the 7-point Ordinal Scale: 1. \- Not hospitalized, no limitations on activities; 2. \- Not hospitalized, limitation on activities; 3. \- Hospitalized, not requiring supplemental oxygen; 4. \- Hospitalized, requiring supplemental oxygen; 5. \- Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. \- Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation; 7. \- Death. |
| Clinical Status of the Patient (According to National Early Warning Score (NEWS Scale)) | Days 1 - 29. | NEWS scale score status, time to a discharge from a hospital or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first. NEWS score is based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse rate, level of consciousness, temperature. A score of 0, 1, 2, 3 is allocated to each parameter except supplemental oxygen (a score 0 or 1 is allocated) and level of consciousness (a score 0 or 3 is allocated). A higher score means the parameter is further from the normal range. All scores were summed to get an aggregate score. Aggregate score ranges from 0 to 19, with higher scores meaning higher risk. Low risk - aggregate score, 1-4 Low to medium risk - score 3 in any single parameter, Medium risk - aggregate score 5-6, High risk - aggregate score 7-19. |
| Number of Patients Requiring Supplementary Oxygen | Days intervals 1 (baseline), 3, 5, 8, 11, 15, 29. | Number of patients requiring supplementary oxygen on Days 3, 5, 8, 11, 15, 29 |
| Hospitalisation Duration | Days 1 - 29 | Duration of hospitalisation |
| Mortality | Days 1 - 29. | Number of participants who were dead or alive (Days 1 - 29) |
| The Number of Participants With Serious Adverse Events | Days 1 - 29. | The number of participants with serious adverse events (SAE) |
| The Number of Participants With Adverse Events | Days 1 - 29. | The number of participants with adverse events (AE) |
| Number of Participants With Discontinuation of Drug Administration | Days 1 - 17. | Number of participants with Permanent or temporary discontinuation of infusions or injections due to adverse events |
Countries
Belarus, Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adult Patients Hospitalized With COVID-19 Patients eligible for enrollment into the study
Polyoxidonium: Polyoxidonium (azoximer bromide) is administered in the dose of 12 mg (contents of 2 vials) once daily intravenously (IV) for 3 days, then every other day intramuscularly (IM) on days 5-17 (the total treatment course is 10 injections) | 81 |
| Total | 81 |
Baseline characteristics
| Characteristic | Adult Patients Hospitalized With COVID-19 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 71 Participants |
| Age, Continuous | 50.88 years STANDARD_DEVIATION 12.81 |
| Baseline severity according to the National Early Warning Score (NEWS Score) Mild (NEWS ≤ 4) | 23 Participants |
| Baseline severity according to the National Early Warning Score (NEWS Score) Severe or Moderate (NEWS = 5…8) | 28 Participants |
| Baseline severity according to the National Early Warning Score (NEWS Score) Very Severe (NEWS ≥ 9) | 30 Participants |
| Basic concomitant medication Anticoagulants | 41 Participants |
| Basic concomitant medication Antimalarial | 37 Participants |
| Basic concomitant medication Antivirals | 46 Participants |
| Mechanical ventilation Absent | 42 Participants |
| Mechanical ventilation Present | 39 Participants |
| News Score (National Early Warning Score) | 6.51 units on a scale STANDARD_DEVIATION 3.41 |
| Ordinal Scale (OS) score | 4.30 units on a scale STANDARD_DEVIATION 1.02 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 77 Participants |
| Region of Enrollment Belarus | 10 participants |
| Region of Enrollment Russia | 71 participants |
| Respiratory support type Invasive lung ventilation | 14 Participants |
| Respiratory support type None | 17 Participants |
| Respiratory support type Non-invasive lung ventilation | 25 Participants |
| Respiratory support type Oxygen therapy | 25 Participants |
| Sex: Female, Male Female | 44 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 81 |
| other Total, other adverse events | 6 / 81 |
| serious Total, serious adverse events | 1 / 81 |
Outcome results
Primary
Clinical Status of the Patient (According to 7-point Ordinal Scale)
Subject clinical status using the 7-point Ordinal Scale, specified as the primary endpoint in the WHO Master Protocol on day 15 as compared to baseline (1 - Not hospitalized, no limitations on activities; 2 - Not hospitalized, limitation on activities; 3 - Hospitalized, not requiring supplemental oxygen; 4 - Hospitalized, requiring supplemental oxygen; 5 - Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6 - Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation; 7 - Death).
Time frame: Day 1 (Baseline), Day 15
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Adult Patients Hospitalized With COVID-19 | Clinical Status of the Patient (According to 7-point Ordinal Scale) | Number of patients at Baseline (Day 1) | 1. Not hospitalized, no limitations on activities | 0 Participants |
| Adult Patients Hospitalized With COVID-19 | Clinical Status of the Patient (According to 7-point Ordinal Scale) | Number of patients at Baseline (Day 1) | 2. Not hospitalized, limitation on activities | 0 Participants |
| Adult Patients Hospitalized With COVID-19 | Clinical Status of the Patient (According to 7-point Ordinal Scale) | Number of patients at Baseline (Day 1) | 3. Hospitalized, not requiring supplemental oxygen | 22 Participants |
| Adult Patients Hospitalized With COVID-19 | Clinical Status of the Patient (According to 7-point Ordinal Scale) | Number of patients at Baseline (Day 1) | 4. Hospitalized, requiring supplemental oxygen | 24 Participants |
| Adult Patients Hospitalized With COVID-19 | Clinical Status of the Patient (According to 7-point Ordinal Scale) | Number of patients at Baseline (Day 1) | 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices | 24 Participants |
| Adult Patients Hospitalized With COVID-19 | Clinical Status of the Patient (According to 7-point Ordinal Scale) | Number of patients at Baseline (Day 1) | 6. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation | 11 Participants |
| Adult Patients Hospitalized With COVID-19 | Clinical Status of the Patient (According to 7-point Ordinal Scale) | Number of patients at Baseline (Day 1) | 7. Death | 0 Participants |
| Adult Patients Hospitalized With COVID-19 | Clinical Status of the Patient (According to 7-point Ordinal Scale) | Number of patients on Day 15 | 1. Not hospitalized, no limitations on activities | 3 Participants |
| Adult Patients Hospitalized With COVID-19 | Clinical Status of the Patient (According to 7-point Ordinal Scale) | Number of patients on Day 15 | 2. Not hospitalized, limitation on activities | 27 Participants |
| Adult Patients Hospitalized With COVID-19 | Clinical Status of the Patient (According to 7-point Ordinal Scale) | Number of patients on Day 15 | 3. Hospitalized, not requiring supplemental oxygen | 37 Participants |
| Adult Patients Hospitalized With COVID-19 | Clinical Status of the Patient (According to 7-point Ordinal Scale) | Number of patients on Day 15 | 4. Hospitalized, requiring supplemental oxygen | 9 Participants |
| Adult Patients Hospitalized With COVID-19 | Clinical Status of the Patient (According to 7-point Ordinal Scale) | Number of patients on Day 15 | 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices | 3 Participants |
| Adult Patients Hospitalized With COVID-19 | Clinical Status of the Patient (According to 7-point Ordinal Scale) | Number of patients on Day 15 | 6. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation | 2 Participants |
| Adult Patients Hospitalized With COVID-19 | Clinical Status of the Patient (According to 7-point Ordinal Scale) | Number of patients on Day 15 | 7. Death | 0 Participants |
p-value: <1e-7Wilcoxon (Mann-Whitney)
Secondary
Clinical Status of the Patient (According to National Early Warning Score (NEWS Scale))
NEWS scale score status, time to a discharge from a hospital or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first. NEWS score is based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse rate, level of consciousness, temperature. A score of 0, 1, 2, 3 is allocated to each parameter except supplemental oxygen (a score 0 or 1 is allocated) and level of consciousness (a score 0 or 3 is allocated). A higher score means the parameter is further from the normal range. All scores were summed to get an aggregate score. Aggregate score ranges from 0 to 19, with higher scores meaning higher risk. Low risk - aggregate score, 1-4 Low to medium risk - score 3 in any single parameter, Medium risk - aggregate score 5-6, High risk - aggregate score 7-19.
Time frame: Days 1 - 29.
Population: Administration of Polyoxidonium was canceled due to Adverse event in 1 patient. Patient received only 2 injections.This is the reason why the needed information for this Outcome Measure is absent for 1 patient.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adult Patients Hospitalized With COVID-19 | Clinical Status of the Patient (According to National Early Warning Score (NEWS Scale)) | 8.85 days | Standard Deviation 6.1 |
Secondary
Hospitalisation Duration
Duration of hospitalisation
Time frame: Days 1 - 29
Population: Administration of Polyoxidonium was canceled due to Adverse event in 1 patient. Patient received only 2 injections.This is the reason why the needed information for this Outcome Measure is absent for 1 patient.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adult Patients Hospitalized With COVID-19 | Hospitalisation Duration | 19.13 days | Standard Deviation 5.29 |
Secondary
Mortality
Number of participants who were dead or alive (Days 1 - 29)
Time frame: Days 1 - 29.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adult Patients Hospitalized With COVID-19 | Mortality | Alive | 81 Participants |
| Adult Patients Hospitalized With COVID-19 | Mortality | Dead | 0 Participants |
Secondary
Number of Participants With Discontinuation of Drug Administration
Number of participants with Permanent or temporary discontinuation of infusions or injections due to adverse events
Time frame: Days 1 - 17.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adult Patients Hospitalized With COVID-19 | Number of Participants With Discontinuation of Drug Administration | Administration of Polyoxidonium was canceled due to Adverse event | 1 Participants |
| Adult Patients Hospitalized With COVID-19 | Number of Participants With Discontinuation of Drug Administration | Administration of Polyoxidonium was postponed by 1 day due to Adverse event | 2 Participants |
Secondary
Number of Patients Requiring Supplementary Oxygen
Number of patients requiring supplementary oxygen on Days 3, 5, 8, 11, 15, 29
Time frame: Days intervals 1 (baseline), 3, 5, 8, 11, 15, 29.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Adult Patients Hospitalized With COVID-19 | Number of Patients Requiring Supplementary Oxygen | Day 3 | Number of patients requiring supplementary oxygen | 58 Participants |
| Adult Patients Hospitalized With COVID-19 | Number of Patients Requiring Supplementary Oxygen | Day 11 | Number of patients requiring supplementary oxygen | 31 Participants |
| Adult Patients Hospitalized With COVID-19 | Number of Patients Requiring Supplementary Oxygen | Baseline (Day 1) | Number of patients requiring supplementary oxygen | 59 Participants |
| Adult Patients Hospitalized With COVID-19 | Number of Patients Requiring Supplementary Oxygen | Baseline (Day 1) | Number of patients not requiring respiratory support | 22 Participants |
| Adult Patients Hospitalized With COVID-19 | Number of Patients Requiring Supplementary Oxygen | Day 3 | Number of patients not requiring respiratory support | 23 Participants |
| Adult Patients Hospitalized With COVID-19 | Number of Patients Requiring Supplementary Oxygen | Day 5 | Number of patients requiring supplementary oxygen | 56 Participants |
| Adult Patients Hospitalized With COVID-19 | Number of Patients Requiring Supplementary Oxygen | Day 5 | Number of patients not requiring respiratory support | 25 Participants |
| Adult Patients Hospitalized With COVID-19 | Number of Patients Requiring Supplementary Oxygen | Day 8 | Number of patients requiring supplementary oxygen | 47 Participants |
| Adult Patients Hospitalized With COVID-19 | Number of Patients Requiring Supplementary Oxygen | Day 8 | Number of patients not requiring respiratory support | 34 Participants |
| Adult Patients Hospitalized With COVID-19 | Number of Patients Requiring Supplementary Oxygen | Day 11 | Number of patients not requiring respiratory support | 50 Participants |
| Adult Patients Hospitalized With COVID-19 | Number of Patients Requiring Supplementary Oxygen | Day 15 | Number of patients requiring supplementary oxygen | 14 Participants |
| Adult Patients Hospitalized With COVID-19 | Number of Patients Requiring Supplementary Oxygen | Day 15 | Number of patients not requiring respiratory support | 67 Participants |
| Adult Patients Hospitalized With COVID-19 | Number of Patients Requiring Supplementary Oxygen | Day 29 | Number of patients requiring supplementary oxygen | 1 Participants |
| Adult Patients Hospitalized With COVID-19 | Number of Patients Requiring Supplementary Oxygen | Day 29 | Number of patients not requiring respiratory support | 80 Participants |
Secondary
The Number of Participants With Adverse Events
The number of participants with adverse events (AE)
Time frame: Days 1 - 29.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adult Patients Hospitalized With COVID-19 | The Number of Participants With Adverse Events | 7 Participants |
Secondary
The Number of Participants With Serious Adverse Events
The number of participants with serious adverse events (SAE)
Time frame: Days 1 - 29.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adult Patients Hospitalized With COVID-19 | The Number of Participants With Serious Adverse Events | 1 Participants |
Secondary
Time to Improvement in Clinical Status of the Patient (According to Ordinal Scale) by 1 Point for Each OS Score
Ordinal scale (OS) score status, time to improvement by 1 point for each OS score. Subject clinical status using the 7-point Ordinal Scale: 1. \- Not hospitalized, no limitations on activities; 2. \- Not hospitalized, limitation on activities; 3. \- Hospitalized, not requiring supplemental oxygen; 4. \- Hospitalized, requiring supplemental oxygen; 5. \- Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. \- Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation; 7. \- Death.
Time frame: Days 1 - 29.
Population: Administration of Polyoxidonium was canceled due to Adverse event in 1 patient. Patient received only 2 injections.This is the reason why the needed information for this Outcome Measure is absent for 1 patient.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adult Patients Hospitalized With COVID-19 | Time to Improvement in Clinical Status of the Patient (According to Ordinal Scale) by 1 Point for Each OS Score | 13.77 days | Standard Deviation 6.01 |