TOFAcitinib Plus Hydroxycloroquine vs Hydroxycloroquine in Patients With Early Onset SARS-CoV2 (COVID-19) Interstitial Pneumonia:a Multicenter Randomized Controlled Open Label Trial
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 116
- 主要终点
- Prevention of severe Respiratory Failure requiring mechanical ventilation
研究概览
简要总结
Multifocal interstitial pneumonia represents the most common cause of admission in intensive care units and death in SARS-CoV2 infections. In our Hospital, similarly to what reported in literature, up to 25% of admitted patients with pneumonitis requires mechanical ventilation or oro-tracheal intubation within 5-10 days. No established treatment is available for this condition. Preliminary evidence is accumulating about the efficacy of an aggressive treatment of the corona virus-induced inflammation and, in particular, investigators believe that blocking JAK1 is clinically rewarding in down-regulating IL-6 driven inflammation in patients with corona-virus infection. Thus, investigators designed a randomized controlled trial to test the hypothesis that adding Tofacitinib to the standard treatment in the early phase of COVID related pneumonitis could prevent the development of severe respiratory failure needing mechanical ventilation.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •SARS-CoV2 Infection diagnosed by rt-PCR
- •CT-scan confirmed interstitial pneumonia
- •Hospital admission from less than 24h
- •P/F ratio >150 mmHg
- •Written Informed Consent
排除标准
- •Age <18 ys or >65
- •Patients in mechanical ventilation at time of admission
- •Severe Hearth failure (NYHA 3 or 4)
- •QTc > 470 ms or >500 ms in wide QRS patients
- •Severe History of Chronic Ischemic Heart Disease, defined as history of Major Adverse Cardiovascular Event and/or recent (one year) revascularization.
- •History of recurrent Deep Venous Thrombosis and Pulmonary Embolism or established thrombophilic conditions (e.g. history of anti-phospholipid antibodies, ...)
- •Active Bacterial or Fungal Infection
- •Hematological cancer
- •Metastatic or intractable cancer
- •Pre-existent neurodegenerative disease
- •Severe Hepatic Impairment,
- •History of acute diverticular disease or intestinal perforation
- •HBsAg positive and/or HBV-DNA positive patients
- •Severe Renal Failure (Creatinine Clearance <30ml/h)
- •Active Herpes zoster infection
- •Patients with active or latent TB
- •Severe anemia (Hb<9g/dl)
- •Lymphocyte count below 750/mcl
- •Neutrophil count below 1000/mcl
- •Platelet count below 50000/mcl
- •Pregnancy or Lactation
- •History of intolerance to the experimental drugs or excipients
- •Degenerative maculopathy or other relevant retinal disease
- •Inability to give informed consent (severe transitory or permanent mental impairment, incapacitation)
研究组 & 干预措施
tofacitinib+HYQ
Tofacitinib 10mg cp twice a day + Hydroxychloroquine 200mg cp three times a day, both for 14 days
干预措施: Tofacitinib (Drug)
tofacitinib+HYQ
Tofacitinib 10mg cp twice a day + Hydroxychloroquine 200mg cp three times a day, both for 14 days
干预措施: Hydroxychloroquine (Drug)
Hydroxychloroquine
Hydroxychloroquine 200mg cp three times a day for 14 days
干预措施: Hydroxychloroquine (Drug)
结局指标
主要结局
Prevention of severe Respiratory Failure requiring mechanical ventilation
时间窗: 14 days
Rate of patients needing mechanical ventilation to maintain PaO2/FIO2\>150
次要结局
- Prevention of need of ICU admission(28 days)
- Prevention of COVID-19 related Deaths(28 days)
- Identification of predictors of outcome(14 days)
- Incidence of Treatment-Emergent Adverse Events(28 days)
研究者
Armando Gabrielli
Full Professor Internal Medicine
Università Politecnica delle Marche