COVID-19 trials registries data warehouse

https://clinicaltrials.gov/show/NCT04832880

Enrico Tombetti, MD, PhD

enrico.tombetti@unimi.it

2021-04-06

Unknown

RCT

Randomized

Parallel

Open label

multi-center

Treatment

inclusion criteria: - adults aged > 18 years able to provide a valid informed consent to the study - documented covid-19 by direct testing (positive pcr), with lung infiltrates at imaging (chest-x ray or ct) and requirement of oxygen supplementation - less than 10 days form symptoms onset - cytokine storm, using the criteria developed at temple university (all of the three below criteria): - crp > 46 mg/l - ferritin > 250 ng/ml - one variable of each of the three clusters below - cluster 1 - albumin < 2.8 g/dl - lymphocytes <10.2 % of wbc - absolute neutrophil count > 11400/mm3 - cluster 2 - alt > 60 u/l - ast > 87 u/l - d-dimers > 4930 µg/l fibrinogen-equivalent-units (feu). - ldh >416 u/l - high sensitivity troponin > 1.09 ng/ml - cluster 3 - anion gap at arterial blood gas < 6.8 mm - chloride > 106 mm - potassium > 4.9 mm - bun:creatinine ratio > 29 - pao2/fio2 200-400 mmhg, while in oxygen therapy or continuous positive airway pressure (c-pap) - for women of childbearing potential and men: agreement to use contraception in the case of heterosexual intercourses before day 28 with a failure rate < 1% per year (bilateral tubal ligation, male sterilisation, hormonal contraceptives inhibiting ovulation, hormone-release or copper intrauterine devices). for men enrolled in the study, condom use is allowed.

- orotracheal intubation or ecmo support - active solid / hematologic cancer (including invasive non-melanoma skin cancer) - hypersensitivity or contra-indications to one of the investigational agents (including history of deep vein thrombosis / pulmonary thromboembolism within 12 weeks prior to screening) - other active concurrent viral, fungal or bacterial infections (including active tuberculosis/latent tb treated for less than 4 weeks, hiv and hcv/hbv infections) - pregnancy/breastfeeding - incapability to provide a valid informed consent (including age < 18 years old) - heart failure with nyha >= 2 or any acute cardiac or vascular event requiring therapy in the previous 12 months - chronic renal failure (baseline gfr < 45 ml/min*1.73m2) - liver cirrhosis moderate / severe (child-pugh b or c) - chronic respiratory failure requiring o2 therapy or ventilation therapy at home - blood neutrophils <1000/mcl, platelet <50000/mcl, hb levels <80 g/l - alt/ast > 5 times unl - use of any biologic agent or small molecule inhibitor and other investigational drugs in the previous 4 weeks or 5 half-lives (whichever is longer). specific cut-offs for wash-out are required for the following therapies: - b-cell targeted therapies: 24 weeks or 5 half-lives (whichever is longer) - tnf-inhibitors: 2 weeks or 5 half-lives (whichever is longer) - jak-inhibitors: 1 week or 5 half-lives (whichever is longer) - use of other immunosuppressive agents in the last 3 months (chronic use of topical steroids and systemic steroids with a dose ≤5 mg of prednisone equivalents is allowed) - use of any other investigational therapy for covid-19 (including iv immunoglobulins, convalescent covid-19 plasma or monoclonal antibodies) - impossibility to discontinue strong inhibitors of oat3 (such as probenecid) at study entry - any other condition judged by the local investigator as a contra-indication to eligibility - subjects who have received live vaccines within 4 weeks before the study or are planned to receive live vaccine in the first months after study enrolment.

4

ASST Fatebenefratelli Sacco

18

100

Italy

Moderate/severe disease at enrollment

4: Moderate/severe disease at enrollment

4000

Prevention of very severe respiratory failure or mortality

None

Phase 3

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