Status:
UNKNOWN
Factorial Randomized Trial of Rendesivir and Baricitinib Plus Dexamethasone for COVID-19 (the AMMURAVID Trial)
Lead Sponsor:
ASST Fatebenefratelli Sacco
Conditions:
Covid19
Eligibility:
All Genders
18+ years
Phase:
PHASE3
Brief Summary
Background: In the current worldwide medical emergency, a rapid identification of effective therapeutic strategy is crucial. So far, therapy with dexamethasone, remdesivir and baricitinib have been a...
Eligibility Criteria
Inclusion
- 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.
- Exclusion criteria:
- 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.
Exclusion
Key Trial Info
Start Date :
April 6 2021
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2022
Estimated Enrollment :
4000 Patients enrolled
Trial Details
Trial ID
NCT04832880
Start Date
April 6 2021
End Date
December 1 2022
Last Update
April 6 2021
Active Locations (21)
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1
Ospedali Riuniti delle Marche
Ancona, Italy
2
Ospedale Parini
Aosta, Italy
3
Ospedale SS Annunziata -Chieti
Chieti, Italy
4
Ospedale S Anna
Como, Italy