An Open Label Phase 1 Trial of Losartan for Worsening Respiratory Illness in COVID-19
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-related Adverse Events as Assessed by Protocol Definition of AE
研究概览
简要总结
This is an open label, phase 1 clinical trial to evaluate the safety of losartan in respiratory failure due to COVID-19.
Briefly, 34 patients with COVID-19 and respiratory failure who meet eligibility criteria and agree to participation in the study will be placed on losartan 25 mg daily on study day 0. If parameters are met the dose of losartan will be increased to 50 mg once daily on study day 3. Participants will continue losartan until they experience resolution of respiratory failure (normal oxygen levels on room air), are discharged from the hospital, meet stoppage criteria (detailed below) or complete 14 days of therapy.
Patients and/or surrogate decision maker who do not give consent to treatment will be asked to allow collection of data from their medical record for use as a control group. We will also collect medical information relating to safety criteria on historical controls treated at the University of Kansas Hospital in the 30 days prior to the study start date and during the study period.
详细描述
This is an open label, phase 1 clinical trial to evaluate the safety of losartan in respiratory failure due to COVID-19.
Clinical Trial setup:
Detailed inclusion and exclusion criteria are listed below. Briefly, 34 patients with COVID-19 and respiratory failure who meet criteria and agree to participation in the study will be placed on losartan 25 mg daily on study day 0. If parameters are met the dose of losartan will be increased to 50 mg once daily on study day 3. Participants will continue losartan until they experience resolution of respiratory failure (normal oxygen levels on room air), are discharged from the hospital, meet stoppage criteria (detailed below) or complete 14 days of therapy.
Patients and/or surrogate decision maker who do not give consent to treatment will be asked to allow collection of data from their medical record for use as a control group.
Stoppage criteria for losartan
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >18 years admitted to the University of Kansas Health System.
- •Confirmation of infection with SARS-CoV-2 by PCR testing.
- •Hypoxic respiratory failure Requiring mechanical ventilation or oxygen OR a SpO2 ≤94% on room air or a PaO2/FiO2 (P/F) ratio <300 OR tachypnea (respiratory rate ≥24 breaths/min). Criteria to be met within 48 hours prior to Day
- •Other concomitant medications such as antivirals and hydroxychloroquine are allowed.
- •Participants prescribed standard of care (SOC) losartan (25mg QD) within 48 hours of consenting may be considered for enrollment if eligibility criteria are met based on EMR data assessment, i.e. no other ARB or ACE prior to SOC medication administration. If participant is eligible and signs consent form, investigational losartan 25mg QD will be ordered to replace SOC prescription on the following scheduled dose.
排除标准
- •Pregnancy.
- •Respiratory failure due to a process other than COVID-
- •Intolerance to ARBs.
- •Previous treatment with an ARB or ACE inhibitor (see exception in inclusion criteria).
- •Current chronic use of medication with known interactions with losartan including NSAIDs (intermittent prior use is acceptable), potassium supplementation aliskiren.
- •Blood pressure less than 90 mm Hg systolic or 60 mm Hg diastolic recorded on at least two readings 30 min apart.
- •Need for vasopressors, unless norepinephrine ≤0.1 µg/kg/min
- •Hyperkalemia (serum K+ >5.5 mM).
- •Known cardiac failure (left ventricular ejection fraction ≤35%), renal insufficiency (Cockcroft-Gault <30 mL/min/1.73 m2 or urinary output <20 mL/h), hepatic failure (LFTs > 5x normal upper limit).
- •Known renal artery stenosis.
- •Neurological, psychiatric, endocrine or neoplastic diseases that are judged to interfere with participation in the study.
- •On another interventional trial (including one for COVID-19) that excludes participation.
研究组 & 干预措施
Open Label Losartan
50 patients with COVID-19 and respiratory failure who meet criteria and agree to participation in the study will be placed on losartan 25 mg once daily on study day 0. If parameters are met the dose of losartan will be increased to 50 mg once daily on study day 3. Participants will continue losartan until they experience resolution of respiratory failure (normal oxygen levels on room air), are discharged from the hospital, meet stoppage criteria or complete 14 days of therapy.
干预措施: Losartan (Drug)
结局指标
主要结局
Number of Participants With Treatment-related Adverse Events as Assessed by Protocol Definition of AE
时间窗: 14 days of losartan treatment
Safety will be reported based on Protocol defined AEs. For the purpose of this protocol, an AE will be defined as as any untoward medical occurrence in a subject during the study listed under DMSB - Anticipated Adverse Events and Grading Scale section of this protocol as well as safety monitoring data listed on protocol table 1 as well as stoppage criteria for losartan. The event does not necessarily have a causal relationship with the treatment. AEs will be collected for both study groups, treatment and control from the time the ICF is signed until the subject completes study participation.
次要结局
- Number of Days on Supplemental Oxygen in Respiratory Failure Due to COVID-19(14 days of losartan treatment)
- Number of Participants With Mechanical Ventilation Use(14 days of losartan treatment)
- Days on Mechanical Ventilation(14 days of losartan treatment)
- Number of Participants With Non-invasive Positive Pressure Ventilation or Heated High Flow Nasal Cannula Use(14 days of losartan treatment)
- Days on Non-invasive Positive Pressure Ventilation or High Flow Nasal Cannula(14 days of losartan treatment)
- Number of Participants With Medications With Possible Antiviral Activity (Hydroxychloroquine, Lopinavir/Ritonavir, Ribavirin or Remdesivir) or Adjunctive Therapy Use (e.g., Tocilizumab)(14 days of losartan treatment)
- Number of Participants With Transfer to ICU From Non-ICU Hospital Bed(14 days of losartan treatment)
- ICU Length of Stay (Days)(14 days of losartan treatment)
- in Hospital Mortality Rate(14 days after study enrollment)
- Hospital Length of Stay (Days)(from enrollment through hospital discharge)
- Cumulative Number of Participants With of Severe Adverse Events(14 days of losartan treatment)
- Number of Participants With Increase of Supplemental Oxygen Needs From Baseline.(14 days of losartan treatment)
- Number of Participants With Extracorporeal Membrane Oxygenation Use(14 days of losartan treatment)
- Number of Participants With Renal Replacement Therapy Use(14 days of losartan treatment)
- Number of Participants With Intolerance to High Dose (50mg) Losartan After Tolerating 25mg(14 days of losartan treatment)
研究者
Matthias Salathe, MD
Professor- University of Kansas Medical Center
University of Kansas Medical Center