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

• ClinicalTrials.gov Identifier: NCT04358081
• Recruitment Status: Completed
• First Posted: April 22, 2020
• Results First Posted: March 17, 2021
• Last Update Posted: October 11, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Covid-19	Drug: HCQ; Drug: HCQ+AZT; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety and Efficacy of Hydroxychloroquine Monotherapy and in Combination With Azithromycin in Patients With Moderate and Severe COVID-19 Disease
• Actual Study Start Date: May 1, 2020
• Actual Primary Completion Date: July 27, 2020
• Actual Study Completion Date: July 27, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm 1: hydroxychloroquine + aithromycin placebo; 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.	Drug: HCQ; Hydroxychloroquine Monotherapy; Other Name: JWT629
Experimental: Arm 2: hydroxychloroquine + azithromycin; 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	Drug: HCQ+AZT; Hydroxychloroquine with azithromycin; Other Name: JWT629 + AZT
Placebo Comparator: Arm 3: hydroxychloroquine placebo + azithromycin placebo; Hydroxychloroquine placebo o.d. (day 1) followed by hydroxychloroquine placebo t.i.d Azythromycin placebo o.d.	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Who Achieved Clinical Response by Day 15 [ Time Frame: 15 days ]
   Clinical response was defined as a) discharged alive; or b) No need for mechanical ventilation in any participants and no need for supplemental oxygen requirement (SpO2) in participants without pre-morbid O2 requirement.

Secondary Outcome Measures :

1. Number of Participants Who Achieved Viral Clearance [ Time Frame: 6 days and 10 Days ]
   Number and percentage of participants with negative or below LLOQ SARS-COV-2 based on polymerase chain reaction (PCR) test
2. Number of Participants Discharged or Ready for Discharge [ Time Frame: 15 days ]
   Number of participants who received hydrochloroquine plus azithromycin relative to placebo who were discharged from hospital
3. Time to Return to Pre-morbid Supplemental Oxygen Requirement in Participants Receiving Hydrochloroquine or Hydrochloroquine Plus Azithromycin Relative to Placebo [ Time Frame: 15 days ]
   Number of participants requiring supplemental oxygen at the time of randomization who returned to pre-morbid supplemental oxygen

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

Novartis Investigative Site

Fullerton, California, United States, 92835

Novartis Investigative Site

Los Angeles, California, United States, 90095-1793

United States, Illinois

Novartis Investigative Site

Chicago, Illinois, United States, 60612

United States, Louisiana

Novartis Investigative Site

Baton Rouge, Louisiana, United States, 70809

United States, Maryland

Novartis Investigative Site

Baltimore, Maryland, United States, 21287

United States, North Carolina

Novartis Investigative Site

Chapel Hill, North Carolina, United States, 27599

United States, Washington

Novartis Investigative Site

Seattle, Washington, United States, 98104

Sponsors and Collaborators

Novartis Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):

Study Protocol  [PDF] April 8, 2020

Statistical Analysis Plan  [PDF] August 13, 2020

More Information

Additional Information:

A Plain Language Trial Summary is available on novartisclinicaltrials.com 

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04358081
• Other Study ID Numbers: CJWT629A12301
• First Posted: April 22, 2020
• Results First Posted: March 17, 2021
• Last Update Posted: October 11, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

covid19; covid 19; covid-19; coronavirus; SARS-CoV; SARS-CoV-2; novel coronavirus; adult; JWT629; acute respiratory syndrome coronavirus

Additional relevant MeSH terms:

COVID-19; Coronavirus Infections; Coronaviridae Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases