Hydroxychloroquine Monotherapy and in Combination With Azithromycin in Patients With Moderate and Severe COVID-19 Disease

Novartis

Status and phase: Completed; Phase 3

Conditions: Covid-19

Treatments: Drug: HCQ; Drug: HCQ+AZT; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04358081

CJWT629A12301

Details and patient eligibility

About

Two recent studies have suggested that in patients with Covid19, treatment with hydroxychloroquine may shorten the duration of symptoms and improve viral clearance, an effect that appears most pronounced when combined with azithromycin. Hydroxychloroquine treatment may inhibit viral nucleic acid-mediated activation of various innate immune pathways, as well as blockade of lysosomal functions in cell types relevant for viral entry and antigen presentation.

The purpose of the study was to determine if oral hydroxychloroquine monotherapy, or in combination with azithromycin results in clinical benefit in patients hospitalized with COVID19 pneumonia.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Informed consent must be obtained prior to participation in the study
2. Adult patient ≥ 18 years old
3. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test from respiratory tract specimen (e.g nasopharyngeal swab)
4. Onset of signs and symptoms of COVID19 illness ≤ 7 days prior to randomization (including but not limited to fever, cough, myalgias, fatigue, abnormal chest imaging)
5. Currently hospitalized or requiring hospitalization due to COVID-19 disease

Exclusion criteria

1. Use of other investigational drugs or newly approved COVID-19 treatments within 5-half lives or 30 days of enrolment
2. History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes
3. Participation in any other clinical trial of an experimental treatment for COVID-19
4. Expectation of concurrent treatment with any other agents or potential direct acting antiviral activity against SARS-Co V-2 during study drug dosing
5. Requires, in the judgement of the investigator, admission to the intensive care unit (ICU) or mechanical ventilatory support (invasive or non-invasive) prior to first dose of study drug (There might be a patient who cannot be admitted to the ICU, even if the patient's condition is severe enough, due to administrative reasons under the current circumstances. This case is also considered under admission to the ICU judged by the investigator)
6. Evidence of cytokine storm syndrome or multi-organ system failure
7. Confirmed co-infection with influenza
8. Creatinine clearance < 45 mL/min or requiring acute renal replacement therapy
9. History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants participating in the study
10. Any other condition which in the opinion of the investigator, would put the safety of the participant at risk, impede compliance or hinder completion of the study
11. Pregnant or nursing (lactating) women
12. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they agree to use basic methods of contraception during dosing of study treatment.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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20 participants in 3 patient groups, including a placebo group

Arm 1: hydroxychloroquine + aithromycin placebo

Experimental group

Description:

Hydroxychloroquine 600mg o.d. as loading dose (Day 1) +followed by 200mg t.i.d was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin (AZT) placebo o.d.

Treatment:

Drug: HCQ

Arm 2: hydroxychloroquine + azithromycin

Experimental group

Description:

Hydroxychloroquine 600 mg o.d. as a loading dose (Day 1) followed by 200 mg t.i.d. was initiated within 8-12 hours of the loading dose (not to exceed 12 hours) Azithromycin: 500 mg as a loading dose (Day 1) followed by 250 mg o.d. Day 2 - Day 5

Treatment:

Drug: HCQ+AZT

Arm 3: hydroxychloroquine placebo + azithromycin placebo

Placebo Comparator group

Description:

Hydroxychloroquine placebo o.d. (day 1) followed by hydroxychloroquine placebo t.i.d Azythromycin placebo o.d.

Treatment:

Drug: Placebo