Efficacy and Safety of Ambervin® and Standard Therapy in Hospitalized Patients With COVID-19
- Conditions
- COVID-19
- Interventions
- Drug: Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate inhaledDrug: Standard of careDrug: Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate intramuscularly
- Registration Number
- NCT05656495
- Lead Sponsor
- Promomed, LLC
- Brief Summary
This is open-labe randomized multicenter comparative Phase III study conducted in 8 medical facilities. The objective of the study is to assess the efficacy, safety and tolerability of Ambervin for intramuscular and inhaled administration in complex therapy COVID-19 compared with the Standard of care (SOC) in hospitalized patients with moderate COVID-19.
- Detailed Description
Upon signing the informed consent form and screening, 313 eligible patients hospitalized with COVID-19 were randomized at a 1:1:1 ratio to receive either Ambervin intramuscular 1mg 1 times a day for 10 days or Ambervin inhaled 10mg 1 times a day for 10 days or SOC.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 313
-
Availability of the Informed Consent Form of thePatient Information Leaflet (PIL) signed and dated bypatient.
-
Men and women aged 18 to 80 years inclusive at thetime of signing the Informed Consent Form in PIL.
-
Confirmed case of COVID-19 at the time ofscreening based on SARS-CoV-2 RNA test usingnucleic acid amplification (NAA) method. It isacceptable to include a patient with a presumptiveCOVID-19 diagnosis prior to receiving the results ofSARS-CoV-2 RNA test made at the screening stage.
-
Hospital admission due to COVID-19.
-
Moderate severity infection with SARS-CoV-2: Clinical signs (the presence of at least 2 of the following criteria):
- body temperature > 38 °C;
- RR > 22/min;
- CT pattern typical of a viral lesion
- shortness of breath on exertion;
- SpO2 < 95%;
- Serum CRP > 10 mg/L.
-
Lesion volume is minimal or moderate; CT 1-2.
-
Patient's consent to use reliable contraceptive methods through out the study and within 1 month for women and 3 months for men after its completion. Reliable means of contraception are: sexualabstinence, use of condom in combination withspermicide.
Women incapable of childbearing may also participate inthe study (with past history of: hysterectomy, tubal ligation,infertility, menopause for more than 2 years), as well asmen with infertility or a history of vasectomy
- Hypersensitivity to components of the study drug.
- Impossibility of CT procedure (for example, gypsumdressing or metal structures in the field of imaging).
- Obstacles or inability to perform intramuscular injections and / or inhalations
- Arterial hypotension (a decrease in blood pressure (BP) below 100/60 mm Hg) at the time of screening and / or a history of hypotensive crises.
- The need for the use of drugs from the list of prohibited therapies.
- Availability of criteria for severe and extremely severe disease at the time of screening
- Presence within 6 months prior to screening of a probable or confirmed case of moderate COVID-19
- History of presumptive or confirmed COVID-19 caseof moderate, severe and extremely severe course ofthe disease.
- Vaccination less than 4 weeks prior to screening.
- The need for treatment in the intensive care unit at the time of screening.
- Impaired liver function (AST and/or ALT ≥ 2 UNLand/or total bilirubin ≥ 1.5 UNL) at the time ofscreening.
- Renal impairment (GFR < 60 ml/min) at the time of screening.
- Positive testing for HIV, syphilis, hepatitis B and/or C.
- Chronic heart failure FC III-IV according to New York Heart Association (NYHA) functional classification.
- Malignancies in the past medical history.
- Alcohol, pharmacological and/or drug addiction in the past medical history and/or at the time of screening.
- Epilepsy in history.
- Schizophrenia, schizoaffective disorder, bipolardisorder, or other history of mental pathology orsuspicion of their presence at the time of screening.
- Severe, decompensated or unstable somatic diseases (any disease or condition that threaten thepatient's life or impair the patient's prognosis, and also make it impossible for him/her to participate in the clinical study).
- Any history data that the investigating physician believes could lead to complication in the interpretation of the study results or create an additional risk to the patient as a result of his/her participation in the study.
- Patient's unwillingness or inability to comply with procedures of the Study Protocol (in the opinion of physician investigator).
- Pregnant or nursing women or women planning pregnancy.
- Participation in another clinical study for 3 monthsprior to inclusion in the study.
- Other conditions that, according to the physicianinvestigator, prevent the patient from being includedin the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ambervin inhaled Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate inhaled Arm 2 (n=105) receives the study drug Ambervin for inhalation administration 10 mg 1 time per day. The course of treatment is 10 days. Standard of care Standard of care Arm 3 (n=104) patients receive standard therapy prescribed in accordance with the recommended treatment regimens included in the InterimGuidelines for the prevention, diagnosis and treatment of new coronavirus infection (COVID-19) approved by the Russian Ministry of Health by decision of the investigator and taking into account the availability of drugs at the study site Ambervin intramuscularly Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate intramuscularly Arm 1 (n=104) receives the study drug Ambervin for intramuscularly administration 1 mg 1 time per day. The course of treatment is 10 days.
- Primary Outcome Measures
Name Time Method Prevalence of patients with category 0-1 as per categorical ordinal clinical improvement WHO scale From baseline to Visit 4 (days 14-15) The proportion of patients with category 0-1 as per the categorical ordinal clinical improvement scale
- Secondary Outcome Measures
Name Time Method Prevalence of patients with clinical status less than 4 points on the categorical ordinal WHO scale of clinical improvement From baseline to Visit 3 (days 11-12) and 4 (days 14-15) The proportion of patients with clinical status less than 4 points on the categorical ordinal WHO scale of clinical improvement
Frequency of improvement in clinical status on a categorical ordinal WHO scale of clinical improvement of 2 or more categories From baseline to Visit 3 (days 11-12) and 4 (days 14-15) The proportion of patients with clinical status on a categorical ordinal WHO scale of clinical improvement of 2 or more categories
Time to improve clinical status on a categorical ordinal scale of clinical improvement by ≥ 1 point. From baseline to Visit 6 (study completion, day 28±1) Number of days to improve clinical status on a categorical ordinal scale of clinical improvement by ≥ 1 point.
Prevalence of patients eligible for discharge to continue outpatient treatment according to BMR From baseline to Visit 2 (days 6-7), 3 (days 11-12) The proportion of patients eligible for discharge to continue outpatient treatment according to current Cuidelines
Prevalence of patients with RR < 22/min From baseline to Visit 2 (days 6-7), 3 (days 11-12) The proportion of patients with RR \< 22/min
Prevalence of patients with CRP level < 10 mg/l From baseline to Visit 2 (days 6-7), 3 (days 11-12) The proportion of patients with CRP level \< 10 mg/l
Prevalence of patients with blood lymphocytes > 1.2 x 10(9)/L From baseline to Visit 2 (days 6-7), 3 (days 11-12) The proportion of patients with blood lymphocytes \> 1.2 x 10(9)/L
Assessment of the degree of lung damage according to CT From baseline to Visit 4 (days 14-15) The degree of lung damage according to CT
Prevalence of patients with SpO2 ≥ 95% on 2 consecutive days From baseline to Visit 2 (days 6-7), 3 (days 11-12), 4 (days 14-15) The proportion of patients with SpO2 ≥ 95% on 2 consecutive days
The frequency of transfer of patients to the intensive care unit and intensive care From baseline to Visit 6 (study completion, day 28±1) The proportion of patients transferred to the intensive care unit and intensive care
The frequency of cases of the use of high flow oxygen therapy, non-invasive and invasive ventilation of lung, ECMO From baseline to Visit 6 (study completion, day 28±1) The proportion of patients who used high flow oxygen therapy, non-invasive and invasive ventilation of lung, ECMO
The frequency of cases of ARDS From baseline to Visit 6 (study completion, day 28±1) The proportion of patients with ARDS
The frequency of patients with a fatal outcome From baseline to Visit 6 (study completion, day 28±1) The proportion of patients with a fatal outcome
Trial Locations
- Locations (10)
Ryazan State Medical University named after academician I.P. Pavlov of Ministry of Health of the Russian Federation
🇷🇺Ryazan, Russian Federation
Voronezh Regional Clinical Hospital No.1
🇷🇺Voronezh, Russian Federation
Infectious Clinical Hospital No.1
🇷🇺Moscow, Russian Federation
Regional Clinical Hospital
🇷🇺Ryazan, Russian Federation
City Hospital No. 40 Kurortny District
🇷🇺Sestroretsk, Russian Federation
Ogarev Mordova State University of Ministry of Health of the Russian Federation
🇷🇺Saransk, Russian Federation
Regional State Budget Healthcare Institution "Clinical hospital No. 1"
🇷🇺Smolensk, Russian Federation
Budgetary institution of the Chuvash Republic "Emergency Hospital"
🇷🇺Cheboksary, Russian Federation
City clinical Hospital №24
🇷🇺Moscow, Russian Federation
State Budgetary Healthcare Institution City Clinical Hospital named after S. I. Spasokukotskiy of Moscow Healthcare Department
🇷🇺Moscow, Russian Federation