Dapagliflozin in Respiratory Failure in Patients With COVID-19
Ключови думи
Резюме
Описание
Recent information on patients at risk for developing serious complications, including death, in the setting of COVID-19, indicate that those with cardiometabolic disease (hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and/or kidney disease at baseline) are at much greater risk. Moreover, a large proportion of these patients develop cardiovascular and/or kidney complications. SGLT2i have previously been demonstrated to have potent heart and kidney-protective effects in patients with type 2 diabetes, heart failure and/or chronic kidney disease, and may afford protection of these vital organ systems in the setting of COVID-19.
Furthermore, both pre-clinical and clinical studies suggest that SGLT2i may favorably impact the underlying mechanistic processes dysregulated in the setting of acute major illness (such as COVID-19) and include favorable effects on endothelial function, inflammation, oxidative stress, tissue hypoxia, energy metabolism and autophagy. These mechanisms have been shown to be important in the setting of respiratory failure, sepsis and multi-organ failure/cytokine storm.
The study population will include hospitalized patients with mild-moderate manifestations of COVID-19 of any duration, but without the need for mechanical ventilation at the time of screening. The eligible patients should have risk-factors for developing serious complications of COVID-19.
It will include patients with a history of at least one of the following: hypertension, T2DM, atherosclerotic cardiovascular disease, HF and/or CKD stage 3 to 4 (eGFR ≥25 mL/min/1.73m2).
Patients will be treated for 30 days, with either dapagliflozin 10 mg daily or placebo, each to be given in addition to the usual standard of care in the participating hospital. Patients will be followed up for an extended additional (observational) period of 60 days (total duration of follow up 90 days) after completing the treatment period.
The study assessments include only those that are absolutely critical for ensuring the safety of the patients, to measure efficacy outcomes, and collect biomarker data, so as not to place too high a burden on the study personnel and to minimize additional risk of exposure to SARS CoV-2.
The primary efficacy endpoint of the study is time to first event of all-cause death or morbid disease complications (respiratory, cardiovascular and kidney) through 30 days of follow-up.
The safety data will be monitored by an Independent Data and Safety Monitoring Committee.
Дати
| Последна проверка: | 05/31/2020 |
| Първо изпратено: | 04/13/2020 |
| Очаквано записване подадено: | 04/13/2020 |
| Първо публикувано: | 04/16/2020 |
| Изпратена последна актуализация: | 06/15/2020 |
| Последна актуализация публикувана: | 06/17/2020 |
| Действителна начална дата на проучването: | 04/21/2020 |
| Приблизителна дата на първично завършване: | 09/30/2020 |
| Очаквана дата на завършване на проучването: | 11/30/2020 |
Състояние или заболяване
Интервенция / лечение
Drug: Dapagliflozin 10mg
Drug: Placebo
Фаза
Групи за ръце
| Arm | Интервенция / лечение |
|---|---|
| Active Comparator: Dapagliflozin 10mg Dapagliflozin 10 mg daily | Drug: Dapagliflozin 10mg Active Comparator: Dapagliflozin 10mg |
| Placebo Comparator: Placebo Dapagliflozin matching placebo 10 mg daily | Drug: Placebo Placebo Comparator |
Критерии за допустимост
| Възрасти, отговарящи на условията за проучване | 18 Years Да се 18 Years |
| Полове, допустими за проучване | All |
| Приема здрави доброволци | Да |
| Критерии | Inclusion Criteria: 1. Provision of informed consent 2. Male or female patients aged ≥18 years 3. Currently hospitalized 4. Hospital admission no more than 4 days prior to screening 5. Confirmed SARS-CoV-2 infection by laboratory testing within 10 days prior to screening, or strongly suspected SARS-CoV-2 infection on presentation 6. Chest radiography or CT findings that, in the opinion of the investigator, are consistent with COVID-19 7. Mild-moderate disease: SpO2≥94% with low-flow supplemental oxygen (5 liters or less) 8. Medical history of at least one of the following: 1. hypertension 2. T2DM 3. atherosclerotic cardiovascular disease 4. heart failure (with either reduced or preserved LVEF) 5. CKD stage 3 to 4 (eGFR between 25 to 60 mL/min/1.73 m2) Key Exclusion Criteria: 1. Severe COVID-19: requiring mechanical ventilation via endotracheal intubation, and/or non-invasive ventilation 2. Expected need for mechanical ventilation within the next 24 hours 3. Expected survival of less than 24 hours at the time of presentation 4. eGFR <25 mL/min/1.73 m2 or receiving renal replacement therapy/dialysis 5. Systolic BP <95 mmHg and/or requirement for vasopressor treatment and/or inotropic or mechanical circulatory support at Screening 6. History of type 1 diabetes mellitus 7. Currently receiving or has received in the last 14 days, experimental immune modulators and/or monoclonal antibody therapies for COVID-19 8. History of diabetic ketoacidosis within last 6 months 9. Current treatment with any SGLT2i (eg, dapagliflozin, canagliflozin, empagliflozin, ertugliflozin) or having received treatment with any SGLT2i within 4 weeks prior to screening 10. Current participation in another interventional clinical trial (with an investigational drug) that is not an observational registry - Note that use of rescue therapies including immune modulators, monoclonal antibody therapies, antiviral therapies, and other agents that are approved or being used through open label compassionate/expanded use programs or in accordance with the local standard of care is permitted during the study. |
Резултат
Първични изходни мерки
1. Time to first occurrence of either death from any cause or new/worsened organ dysfunction through 30 days of follow up, defined as at least one of the following: [Randomization through Day 30]
Вторични изходни мерки
1. Hierarchical composite outcome measures including time to death from any cause, time to new/worsened organ dysfunction, clinical status at day 30 and time to hospital discharge [Randomization through Day 30]
2. Time to hospital discharge [Randomization through Day 30]
3. Total number of days alive, out of hospital, and/or free from mechanical ventilation [Randomization through Day 30]
4. Total number of days alive, not in the ICU, and free from mechanical ventilation (as defined in the primary outcome measure) [Randomization through Day 30]
5. Time to death from any cause [Randomization through Day 30]
6. Time to new/worsened organ dysfunction [Randomization through Day 30]
7. Time to acute kidney injury (defined as doubling of s-Creatinine compared to baseline) [Randomization through Day 30]
