Treatment of COVID19 : a randomised controlled trial

INTERVENTION: Intervention1: Hydroxychloroquine sulfate (HCQs): HCQ 400mg BD on D1 and 400 mg OD on D2 ‐ 5 Intervention2: Hydroxychloroquine sulphate high dose HCQh): HCQ 600 mg BD on D1 and 600 mg OD on D2 ‐ 5 Intervention3: HCQ high dose (HCQh): HCQ 600mg BD D1 HCQ 300mg BD D2 ‐ D5 Control Intervention1: HCQ AZT: HCQ 400mg BD AZT 500mg OD D1 HCQ 400mg OD AZT 250 mg OD D2 ‐ D5 CONDITION: Health Condition 1: B972‐ Coronavirus as the cause of diseases classified elsewhere Health Condition 2: B338‐ Other specified viral diseases PRIMARY OUTCOME: COVID Ordinal Outcomes Scale is defined as: ; 1. Death ; 2. Hospitalised on invasive mechanical ventilation or extracorporeal mechanical ventilation ( ECMO) ; 3. Hospitalised on non‐invasive ventilation or high‐flow nasal cannula oxygen therapy ; 4. Hospitalised on supplemental oxygen ; 5. Hospitalised not on supplemental oxygen ; 6. Not hospitalised with limitation of activity (due to continued symptoms) ; 7. Not hospitalised without limitation in activity (no symptoms)Timepoint: D14 ; SECONDARY OUTCOME: All location, all‐cause mortality assessed on D14 (Time frame‐ assessed on 14th day of starting treatment) Vital status of patient will be ascertained from medical record review, phone call to patient or proxy ; Timepoint: D14 All location, all‐cause mortality on D28 (Time frame‐ assessed on 28th day of starting treatment) Vital status of patient will be ascertained from medical record. review, phone call to patient or proxy ; Timepoint: D28 Compare groups with regards to acute kidney injury to D28 (The number of patients who have acute kidney injury between starting treatment and 28th day will be determined) ; Timepoint: D28 Compare groups with regards to acute pancreatitis to D28 (The number of patients who have acute pancreatitis between starting treatment and 28th day will be determined) ; Timepoint: D28 Compare groups with regards to atrial or ventricular arrhythmia to D28 (The number of patients who have atrial or ventricular arrhythmias between starting treatment and 28th day will be determined) ; Timepoint: D28 Compare groups with regards to cardiac arrest to D28 (The number of patients who have cardiac arrests between starting treatment and 28th day will be determined) ; Timepoint: D28 Compare groups with regards to elevation of aspartate aminotransferase to D28 (The number of patients who have aspartate aminotransferase level more than two times upper limit of normal between starting treatment and 28th day will be determined) ; Timepoint: D28 Compare groups with regards to neutropenia, lymphopaenia, anaemia or thrombocytopenia to D28 (The number of patients who have neutropenia, lymphopaenia, anaemia or thrombocytopenia between starting treatment and 28th day will be determined) ; Timepoint: D28 Compare groups with regards to seizures to D28 (The number of patients who have seizures between starting treatment and 28th day will be determined) ; Timepoint: D28 Compare groups with regards to severe dermatologic reaction to D28 (The number of patients who experience severe dermatologic reaction between starting treatment and 28th day will be determined)Timepoint: D28 Compare groups with regards to symptomatic hypoglycaemia to D28 (The number of patients who experience symptomatic hypoglycaemia between starting treatment and 28th day will be determined) ; Timepoint: D28 COOS on D28 (COOS will be determined for all patients on 28th day day of starting treatment) ; Timepoint: D28 COOS on D7 (COOS will be determined for all patients on 7th day of starting treatment) ; Timepoint: D7 COVID Ordinal Outcomes Scale on D2 (COOS will be determined for all patients on 2nd day of starting treatment). ; Timepoint: D2 Hospital‐free days through D28 (28th day of starting treatment. Hospital free days is defined as 28 minus the number of days from enrolment to discharge to home. If patient has not been discharged to home by D28 or dies during hospitalisation, he will be assigned a value of zeroTimepoint: D28 ICU‐free days through D28 (28th day of starting treatment. ICU free days is defined as 28 minus the duration of ICU days through the 28 days. Patients not surviving up to D28 will be assigned a ICU‐free days value of zero.) ; Timepoint: D28 Number of patients receiving renal replacement therapy to D28 (The number of patients who receive renal replacement therapy between starting treatment and 28th day will be determined) ; Timepoint: D28 Oxygen‐free days through D28 (28th day of starting treatment). Oxygen‐free days is defined as 28 minus the duration of days through the 28 days when he received Oxygen therapy. Patients not surviving up to D28 will be passing a ventilator‐free days value of zero.) ; Timepoint: D28 Vasopressor‐free days through D28 (28th day of starting treatment. Vasopressor free days is defined as 28 minus the duration of vasopressor support days through the 28 days. Patients not surviving up to D28 will be assigned a vasopressor‐free days value of zero.) ; Timepoint: D28 Ventilator‐free days through D28 (28th day of starting treatment. Ventilator free days is defined as 28 minus the duration of ventilated days through the 28 days. Patients not surviving up to D28 will be assigned a ventilator‐free days value of zero.) ; Timepoint: D28 INCLUSION CRITERIA: Age > 18 years All sexes Case definitions for inclusion in the study will include mild, moderately severe and severe cases as defined in the Guidance on appropriate treatment of suspect/confirmed case of COVI19 issued by Ministry of Health and Family Welfare, Govt of India on 07 Apr 2020. Mild: Cases presenting with fever and/or upper respiratory tract illness (Influenza like Illness, ILI) Moderate: Pneumonia with no signs of severe disease (Respiratory Rate 15 to 30/minute, SpO2 90%‐94%). Severe: Severe Pneumonia (with respiratory rate â?Â¥30/minute and/or SpO2 < 90% in room air) or ARDS or septic shock Laboratory confirmed SARS CoV‐2 infection within last 10d or SARS CoV‐2 test result pending with a high clinical suspicion as defined by: Cough of <10d duration Bilateral pulmonary infiltrates on chest X Ray / CT scan or new hypoxaemia defined as SpO2 <9