COVID-19
Conditions
Interventions
Trade Name: Plaquenil
Product Name: Idrossiclorochina
Product Code: [Idrossiclorichina]
Pharmaceutical Form: Tablet
INN or Proposed INN: IDROSSICLOROCHINA SOLFATO
Current Sponsor code: idrossiclorochi
Sponsors
SOCIETA' ITALIANA MALATTIE INFETTIVE E TROPICALI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Adults aged >= 18 years able to provide a valid informed consent to the study • Documented COVID-19 according to local requirements, with pneumonia at imaging (Chest-X ray or CT) • High inflammation, one of the following: ¿ CRP > 6 times UNL ¿ D-dimer > 1500 ng/ml • PaO2/FiO2 250-400 mmHg Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 800 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 600
Exclusion criteria
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 or diverticulitis) • Other active concurrent viral, fungal or bacterial infections (including active tuberculosis, HIV and HCV/HBV infections) • Pregnancy/breastfeeding • Incapability to provide a valid informed consent (including age = 2 or any acute cardiac or vascular event requiring therapy in the previous 12 months • Chronic renal failure (baseline GFR 5 times UNL • Use of any biologic agent or small molecule inhibitor and other investigational drugs in the previous 3 months (or 5 half-lives) • Use of other immunosuppressive agents in the last 3 months • Any other condition judged by the local investigator as a contra-indication to eligibility
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this nation-wide randomised trial is to assess whether immunosuppressive agents in addition to hydroxicloroquine can reduce the progression to very severe respiratory failure with PaO2/FiO2 ratio < 200 mmHg (ARDS-range).;Secondary Objective: The secondary objectives are to assess any effects of these immunomodulatory drugs on surrogate markers of COVID-19 severity and course with particular attention towards modelling kinetics of markers of immune response associated with disease evolution. Another secondary objective is to verify the safety of the immunomodulatory agents for during COVID-19. Surrogate markers of COVID-19 course will include: a) Clinical deterioration, defined as at least one of the following: • Death • Need of orotracheal intubation/ECMO • Increase in NEWS-2 score ¿ 2 from baseline • Increase in MELD score ¿ 8 from baseline b) Mortality c) Need of orotracheal intubation or ECMO d) Evolution of NEWS-2 and MELD scores e) Clinical improvement, defined as one of the following • Discharge • Absent ventilator support, NEWS-2 score =3 and MELD =13 f) Discharge g) Defervescence h) Course of blood tests and PaO2/FiO2;Primary end point(s): Proportion of patients with PaO2/FiO2 <200 mmHg at day 10 in each intervention arm as compared to the control arm ;Timepoint(s) of evaluation of this end point: Day 10 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of patients with PaO2/FiO2 37°C, without recurrent T>37.0° for at least 4 days) at day 7, 10, 14, 21, 28 of each interventional arm as compared to the control arm • Comparison of the time to persistent defervescence (last day of T>37°C, without recurrent T>37.0° for at least 4 days) of each interventional arm as compared to the control arm • Proportion of patients discharged at day 7, 10, 14, 21, 28 of each interventional arm as compared to the control arm • Time to discharge of each interventional arm as compared to the control arm • Comparison of the course of blood test in the different arms: ¿ FBC ¿ Creatinine ¿ Bilirubin ¿ Albumin ¿ LDH ¿ AST/ALT ¿ CK ¿ CRP ¿ IL-6 ¿ troponin T ¿ ferritin ¿ prothrombin-time (INR) ¿ lipid profile (triglycerides, HDL-cholesterol, TOTAL-cholesterol) ¿ D-dimer ¿ PaO2 (arterial gas analysis) and PaO2/FiO2 ;Timepoint(s) of evaluation of this end point: Day 7, 10, 14, 21, 28 | — |
Countries
Italy
Contacts
Public ContactMalattie Infettive
AOUI VERONA
Outcome results
None listed