NCT04452565.

Study name	NA‐831, atazanavir and dexamethasone combination therapy for the treatment of COVID‐19 infection (NATADEX)
Methods	Trial design: phase 2/3, triple‐blinded (care provider, investigator, outcomes assessor), RCT Sample size: 525 Setting: inpatient Language: English Number of centres: 31 Type of intervention (treatment/prevention): treatment
Participants	Inclusion criteria Hospitalisation for management of SARS CoV‐2 infection Positive SARS CoV‐2 test Age ≥ 18 years Provision of informed consent ECG ≤ 48 h prior to enrolment Complete blood count, glucose‐6 phosphate‐dehydrogenase (G6PD), comprehensive metabolic panel and magnesium ≤ 48 h prior to enrolment from standard care If participating in sexual activity that could lead to pregnancy, individuals of reproductive potential who can become pregnant must agree to use contraception throughout the study. At least one of the following must be used throughout the study: condom (male or female) with or without spermicide, diaphragm or cervical cap with spermicide, intrauterine device (IUD), hormone‐based contraceptive Exclusion criteria Contraindication or allergy to NA‐831, atazanavir, dexamethasone Current use any antiviral drug or anti‐inflammatory drug Concurrent use of another investigational agent IMV Participants who have any severe and/or uncontrolled medical conditions such as: Unstable angina pectoris Symptomatic congestive heart failure Myocardial infarction Cardiac arrhythmias or Known prolonged QTc > 470 men, > 480 women on ECG pulmonary insufficiency Epilepsy (interaction with chloroquine) Prior retinal eye disease Concurrent malignancy requiring chemotherapy Known chronic kidney disease, eGFR < 10 or dialysis, G‐6‐PD deficiency, if unknown requires G6PD testing prior to enrolment Known porphyria Known myasthenia gravis Currently pregnant or planning on getting pregnant while on study Breastfeeding AST/ALT > 5 x ULN Bilirubin > 5 x ULN Magnesium < 1.4 mEq/L Calcium < 8.4 mg/dL > 10.6 mg/dL Potassium < 3.3 > 5.5 mEg/L
Interventions	Arm 1: NA‐831 30 mg orally twice a day for 1 day, followed by 30 mg once day for 4 consecutive days (5 days in total) Arm 2: NA‐831 60 mg orally twice a day for 1 day, followed by 30 mg once a day for 4 consecutive days (5 days in total). The drug will be supplied in 30 mg capsule AND atazanavir 400 mg orally twice a day for 1 day, followed by 200 mg daily for 4 consecutive days (5 days total). Arm 3: NA‐831 60 mg orally twice a day for 1 day, followed by 30 mg once a day for 4 consecutive days (5 days in total) AND dexamethasone 8 mg orally twice a day for 1 day, followed by 4 mg daily for 4 consecutive days (5 days total) Arm 4: atazanavir 400 mg orally twice a day for 1 day, followed by 200 mg daily for 4 consecutive days (5 days total) AND dexamethasone 8 mg orally twice a day for 1 day, followed by 4 mg daily for 4 consecutive days (5 days total). The drug will be supplied in 4 mg tablets.
Outcomes	Primary outcome Time (hours) from randomisation to recovery defined as: absence of fever, as defined as at least 48 h since last temperature ≥ 38.0 °C without the use of fever‐reducing medications; AND absence of symptoms of > mild severity for 24 h; AND not requiring supplemental oxygen beyond pre‐COVID baseline; AND freedom from mechanical ventilation or death (time frame: 36 days).
Starting date	First posted: 30 June 2020
Contact information	Brian Tran, MD: 1‐415‐941‐3133  Email: BTran@neuroactiva.com
Notes	Recruitment status: recruiting Prospective completion date: 15 February 2021 Date last update was posted: 7 September 2020 Sponsor/funding: NeuroActiva, Inc.