Trial of Early Therapies During Non-hospitalized Outpatient Window (TREAT NOW) for COVID-19
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 452
- 试验地点
- 6
- 主要终点
- Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group)
研究概览
简要总结
Blinded, multicenter, placebo-controlled, randomized clinical trial evaluating lopinavir/ritonavir vs placebo in early outpatient treatment of adults with COVID-19
详细描述
We will conduct an investigator-initiated, multicenter, blinded, placebo-controlled, randomized clinical trial evaluating lopinavir/ritonavir vs placebo for early treatment of adults with COVID-19 in the outpatient setting prior to hospitalization. Patients, treating clinicians, and study personnel will all be blinded to study group assignment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Lopinavir/Ritonavir tablets or unmatched placebo tablets
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
- •Laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by reverse transcription polymerase chain reaction (RT-PCR) or other molecular test collected within the past 6 days
- •Current symptoms of acute respiratory infection for ≤6 days, defined as one or more of the following: cough, fever, shortness of breath, chest pain, abdominal pain, nausea/vomiting, diarrhea, body aches, weakness/fatigue.
排除标准
- •Breast feeding
- •Two individuals from the same household are not enrolled in the study
- •Unable to randomize within 6 days after onset of acute respiratory infection symptoms
- •Hospitalization within the 6 days prior to randomization
- •Inability to swallow oral medications
- •Refusal or inability to be contacted and participate in daily symptom/safety monitoring in English or Spanish during the two-week follow-up period
- •Previous enrollment in this trial
- •Known severe chronic kidney disease requiring dialysis
- •Known severe liver disease [cirrhosis or >3 times upper limit of normal for aspartate aminotransferase (AST) or alanine aminotransferase (ALT) in medical record if available]
- •Known hepatitis B or hepatitis C infection
- •Known history of jaundice
- •Current heavy alcohol use, defined as 8 drinks or more per week for women or 15 drinks or more per week for men
- •Known seizure disorder
- •Known human immunodeficiency virus (HIV) infection
- •Known history of pancreatitis
- •Known history of prolonged QT interval [Long QT Syndrome, patient report, or corrected QT interval (QTc) >500 milliseconds on most recently available electrocardiogram within the past 2 years]
- •Receipt of >1 dose of lopinavir/ritonavir in the 10 days prior to enrollment
- •Known allergy to lopinavir/ritonavir
- •Currently prescribed (with planned continuation) or planned administration during 14-day study period of medication at high risk for QT prolongation as follows:
- •Antiarrhythmics: Amiodarone, disopyramide, dofetilide, dronedarone, flecainide, ibutilide, procainamide, propafenone, quinidine, sotalol Anti-cancer: Arsenic trioxide, oxaliplatin, vandetanib Antidepressants: Amitriptyline, citalopram, escitalopram, imipramine Antimicrobials: azithromycin, ciprofloxacin, clarithromycin, erythromycin, fluconazole, levofloxacin, moxifloxacin, pentamidine, hydroxychloroquine Antipsychotics: haloperidol, chlorpromazine, droperidol, olanzapine, pimozide, quetiapine, thioridazine, risperidone, ziprasidone Others: cilostazol, cimetidine, cisapride, donepezil, methadone, ondansetron, sumatriptan
- •Currently prescribed (with planned continuation) or planned administration during 14-day study period of any of the following medications: alfuzosin, apalutamide, astemizole, ergot-containing medicines (including dihydroergotamine mesylate, ergotamine tartrate, methylergonovine), lomitapide, lovastatin, lurasidone, midazolam, phenobarbital, phenytoin, ranolazine, rifampin, sildenafil, simvastatin, St. John's Wort, terfenadine, triazolam. Patients who are on warfarin or fluticasone will be advised to contact their primary care provider to advise them that they are in the trial and possibly receiving lopinavir/ritonavir which can influence levels of either drug and may require more frequent monitoring.
研究组 & 干预措施
Group 1 - Lopinavir/Ritonavir
Lopinavir/Ritonavir 400 mg/100 mg orally twice daily for twenty-eight doses (Days 1-14)
干预措施: Lopinavir/Ritonavir 400 mg/100 mg (Drug)
Control Group
Placebo unmatched orally twice daily for 14 days
干预措施: Placebo (Other)
结局指标
主要结局
Modified COVID Ordinal Outcomes Scale: Study Day 15 (Group 2 and Placebo Control Group)
时间窗: Day 1 to Day 15
Improvement of clinical condition of the participant defined by the Modified COVID Ordinal Outcomes Scale (Modified from the COVID-19 WHO ordinal Outcomes score to fit the outpatient setting). This scale reflects a range of participants from dead to not hospitalized and with no limitations to activities of daily living. A score of 1 is "death", 2 is "Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO)", 3 is "Hospitalized on supplemental oxygen", 4 is "Hospitalized not on supplemental oxygen", 5 is "Not hospitalized with symptoms and limitation in activity", 6 is "Not hospitalized with symptoms but with no limitation in activity", 7 is "Not hospitalized without symptoms nor limitation in activity". COVID outcomes are more severe at the lower end of the scale and milder at the higher end of the scale for this outpatient trial.
次要结局
- Number of Patients Hospitalized: Day 1 to 29 (Group 2 and Placebo Control Group)(Day 1 to Day 29)
- Fever-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)(Day 1 to Day 29)
- Hospital-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)(Day 1 to Day 29)
- Modified COVID Ordinal Outcome Scale: Study Day 8 (Group 2 and Placebo Control Group)(on or at Day 8)
- Modified COVID Ordinal Outcome Scale: Study Day 29 (Group 2 and Placebo Control Group)(on or at Day 29)
- All-cause, All-location Mortality: Day 1 to Day 29 (Group 2 and Placebo Control Group)(Day 1 to Day 29)
- Ventilator-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)(Day 1 to Day 29)
- Time to Hospitalization Day 1 to Day 29 (Group 2 and Placebo Control Group)(Day 1 to Day 29)
- Time to Symptom Resolution: Day 1 to Day 29 (Group 2 and Placebo Control Group)(Day 1 to Day 29)
- Oxygen-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)(Day 1 to Day 29)
- ICU-free Days: Day 1 to Day 29 (Group 2 and Placebo Control Group)(Day 1 to Day 29)
- Vasopressor-free Days Through Study Day 29 (Group 2 and Placebo Control Group)(Day 1 to Day 29)
研究者
Todd Rice
Associate Professor of Medicine
Vanderbilt University Medical Center