Clinical trial NCT04527133: An Open Non-comparative Study of the Efficacy and Safety of Aprotinin in Patients Hospitalized With COVID-19
Official title: An Open Non-comparative Study of the Efficacy and Safety of Aprotinin in Patients Hospitalized With COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: COVID-19
Keywords: COVID-19
SARS-CoV-2
pneumonia
inpatients
Lead sponsor: Aviron LLC
Sponsor class: INDUSTRY
First posted: 2020-08-26
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: A non-comparative study of the efficacy and safety
Primary purpose: TREATMENT

Brief summary: The observational study will be carried out in two stages. At the first stage, the efficacy and safety of Aprotinin intravenous infusion as add-on therapy to the standard of care will be studied. At the second stage, two groups will be included: the first group will be the inhaled Aprotinin add-on therapy, the second group will be intravenous Aprotinin in combination with Favipiravir.

Detailed description: Primary objective of the study is to evaluate the efficacy of Aprotinin as add-on therapy in patients hospitalized with COVID-19 using the following parameters:

* The time to elimination of SARS-CoV-2 virus until Day 10;
* The time to C-reactive protein (CRP) normalization until Day 10;
* The time to D-dimer normalization until Day 10.

Secondary objectives are to evaluate the following parameters of efficacy and safety of Aprotinin add-on therapy in patients hospitalized with COVID-19:

* The time to body temperature normalization (\<37oC);
* Changes from baseline of the laboratory parameters during 14 days: hematology, CRP, coagulogram;
* Changes of lung injury on CT scan on Day 7 and Day 14 from baseline;
* Frequency of clinical status improvement by 2 scores in accordance with the WHO Ordinal scale of clinical improvement (WHO-OSCI) or discharge from the hospital before Day 14;
* Frequency of transfer to the Intensive Care Unit (ICU), frequency of the non-invasive ventilation, frequency of the invasive ventilation and mortality rate;
* Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) of various severity according to subjective complains, physical examination, vital signs, laboratory tests and ECG.

Eligibility criteria: Inclusion Criteria:

1. Signed Patient Information Sheet and Informed Consent Form for participation in the study;
2. Adult male or female ≥18 years of age;
3. Body mass \< 90 kg;
4. Positive qualitative RNA SARS-CoV-2 PCR analysis at screening;
5. Score 4 on the WHO-OSCI (added at Stage 2);
6. Subjects with moderate-to-severe disease with the follow conditions and symptoms:

   * Pneumonia;
   * Fever \> 38°C;
   * Blood serum CRP \> 10 mg/L.
7. Agreement to use medically acceptable forms of birth control during the study (contraceptive with spermicide).

Exclusion Criteria:

1. Severe disease with one of the follow criteria:

   * Respiratory rate \> 35 per minute that doesn't decrease after body temperature reducing to normal or subfebrile level;
   * Saturation ≤ 93% at rest;
   * Partial pressure of arterial oxygen (PaO2) \< 60 mmHg;
   * Oxygenation index (РаО2/FiO2) ≤ 200 mmHg;
   * Partial pressure of arterial CO2 (PaCO2) \> 60 mmHg;
   * Septic shock.
2. Chronic liver and kidney diseases in terminal stage;
3. Other organs failure requiring control and treatment in the ICU;
4. Subjects with HIV;
5. Using of Aprotinin during 6 months prior to screening; hypersensitivity to any of the drug components;
6. Participation in any other clinical trial or using of other study drugs during 28 days prior to screening;
7. Pregnant or lactating women or women planning pregnancy during the clinical study; women with child-bearing potential (including women non-sterilized surgically and in postmenopause for less than 2 years) not using medically acceptable forms of birth control;
8. Inability to read or write; unwillingness to understand and follow the Protocol procedures; non-compliance with the regimen of taking medications or performing procedures that, according to the Investigator, may affect the results of the study or the safety of the patient and prevent the patient from further participation in the study; any other comorbid medical or serious mental conditions that make patient ineligible for participation in the clinical study, limits the ability to obtain informed consent, or may affect patient's ability to participate in the study.

Primary outcomes:
measure: Time to elimination of SARS-CoV-2 virus
timeFrame: 10 days
measure: Time to CRP normalization
timeFrame: 10 days
measure: Time to D-dimer normalization
timeFrame: 10 days
Secondary outcomes:
measure: Time to body temperature normalization
timeFrame: 14 days
measure: Change in absolute neutrophil count (ANC)
timeFrame: Baseline to Day 14
measure: Change in white blood cells (WBC)
timeFrame: Baseline to Day 14
measure: Change of CRP
timeFrame: Baseline to Day 14
measure: Change of D-dimer
timeFrame: Baseline to Day 14
measure: Change in fibrinogen
timeFrame: Baseline to Day 14
measure: Change of Quick's value
timeFrame: Baseline to Day 14
measure: Change of international normalized ratio (INR)
timeFrame: Baseline to Day 14
measure: Changes of lung injury on CT scan
timeFrame: Baseline to Day 14
measure: Frequency of clinical status improvement by 2 scores in accordance with the WHO-OSCI or discharge from the hospital
timeFrame: 14 days
measure: Frequency of deterioration of the patients' status
timeFrame: 14 days
measure: Frequency of AEs and SAEs
timeFrame: 14 days
Other outcomes:
Locations:
city: Smolensk
country: Russian Federation
facility: Regional State Budgetary Healthcare Institution "Clinical Hospital №1"
Study officials:
affiliation: Clinical Hospital #1, Smolensk
name: Elena Simakina, MD
role: PRINCIPAL_INVESTIGATOR
References: