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NCT04358081

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

Completed Phase 3 Results posted Last updated 11 October 2021
What this trial tests

Phase 3 trial testing HCQ in Covid-19 in 20 participants. Completed in 27 July 2020.

Timeline
1 May 2020
Primary endpoint
27 July 2020
27 July 2020

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment20
Start date1 May 2020
Primary completion27 July 2020
Estimated completion27 July 2020
Sites7 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Covid-19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Achieved Clinical Response by Day 15 Primary · 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.

GroupValue95% CI
Arm 1: Hydroxychloroquine + Aithromycin Placebo7
Arm 2: Hydroxychloroquine + Azithromycin7
Arm 3: Hydroxychloroquine Placebo + Azithromycin Placebo4
Number of Participants Who Achieved Viral Clearance Secondary · 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

by 6 days
GroupValue95% CI
Arm 1: Hydroxychloroquine + Aithromycin Placebo2
Arm 2: Hydroxychloroquine + Azithromycin3
Arm 3: Hydroxychloroquine Placebo + Azithromycin Placebo3
by 10 days
GroupValue95% CI
Arm 1: Hydroxychloroquine + Aithromycin Placebo2
Arm 2: Hydroxychloroquine + Azithromycin3
Arm 3: Hydroxychloroquine Placebo + Azithromycin Placebo3
Number of Participants Discharged or Ready for Discharge Secondary · 15 days

Number of participants who received hydrochloroquine plus azithromycin relative to placebo who were discharged from hospital

GroupValue95% CI
Arm 1: Hydroxychloroquine + Aithromycin Placebo7
Arm 2: Hydroxychloroquine + Azithromycin7
Arm 3: Hydroxychloroquine Placebo + Azithromycin Placebo4
Time to Return to Pre-morbid Supplemental Oxygen Requirement in Participants Receiving Hydrochloroquine or Hydrochloroquine Plus Azithromycin Relative to Placebo Secondary · 15 days

Number of participants requiring supplemental oxygen at the time of randomization who returned to pre-morbid supplemental oxygen

GroupValue95% CI
Arm 1: Hydroxychloroquine + Aithromycin Placebo7
Arm 2: Hydroxychloroquine + Azithromycin6
Arm 3: Hydroxychloroquine Placebo + Azithromycin Placebo4

Adverse events — posted to ClinicalTrials.gov

Time frame: at day 15. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Hydroxychloroquine + Aithromycin Placebo
Serious: 1/7 (14%)
Deaths: 0/7
Hydroxychloroquine + Azithromycin
Serious: 0/7 (0%)
Deaths: 0/7
Hydroxychloroquine Placebo + Azithromycin Placebo
Serious: 2/5 (40%)
Deaths: 1/5
Total
Serious: 3/19 (16%)
Deaths: 1/19

Serious adverse events (4 terms)

ReactionSystemHydroxychloroquine + Aithr…Hydroxychloroquine + Azith…Hydroxychloroquine Placebo…Total
Cardiac arrestCardiac disorders
Acute kidney injuryRenal and urinary disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
TachypnoeaRespiratory, thoracic and mediastinal disorders
Other adverse events (39 terms — click to expand)

ReactionSystemHydroxychloroquine + Aithr…Hydroxychloroquine + Azith…Hydroxychloroquine Placebo…Total
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
HeadacheNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Intracardiac massCardiac disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
VomitingGastrointestinal disorders
Chest discomfortGeneral disorders
Chest painGeneral disorders
ChillsGeneral disorders
PainGeneral disorders
PyrexiaGeneral disorders
Blood bilirubin increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations
Blood triglycerides increasedInvestigations
Electrocardiogram QT prolongedInvestigations
Hepatic enzyme increasedInvestigations
Neutrophil percentage increasedInvestigations
Urine analysis abnormalInvestigations
HypercholesterolaemiaMetabolism and nutrition disorders
HyperkalaemiaMetabolism and nutrition disorders
Vitamin B12 deficiencyMetabolism and nutrition disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
DysgeusiaNervous system disorders
Feeling of despairPsychiatric disorders
InsomniaPsychiatric disorders
Acute kidney injuryRenal and urinary disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Pleuritic painRespiratory, thoracic and mediastinal disorders
Night sweatsSkin and subcutaneous tissue disorders
HypotensionVascular disorders

Most-reported serious reactions: Cardiac arrest, Acute kidney injury, Hypoxia, Tachypnoea.

Data from ClinicalTrials.gov NCT04358081 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts.
    Wang J, Jiang M, Chen X, Montaner LJ. · · 2020 · cited 551× · PMID 32534467 · DOI 10.1002/jlb.3covr0520-272r
  2. COVID-19: Characteristics and Therapeutics.
    Chilamakuri R, Agarwal S. · · 2021 · cited 192× · PMID 33494237 · DOI 10.3390/cells10020206
  3. An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment.
    Drożdżal S, Rosik J, Lechowicz K, Machaj F, et al · · 2021 · cited 186× · PMID 34991982 · DOI 10.1016/j.drup.2021.100794
  4. Multicenter Interim Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2.
    Chiotos K, Hayes M, Kimberlin DW, Jones SB, et al · · 2021 · cited 74× · PMID 32918548 · DOI 10.1093/jpids/piaa115
  5. Antibiotics for the treatment of COVID-19.
    Popp M, Stegemann M, Riemer M, Metzendorf MI, et al · · 2021 · cited 60× · PMID 34679203 · DOI 10.1002/14651858.cd015025
  6. Tackling SARS-CoV-2: proposed targets and repurposed drugs.
    Joshi S, Joshi M, Degani MS. · · 2020 · cited 41× · PMID 32564623 · DOI 10.4155/fmc-2020-0147
  7. Therapeutic Potential of Exploiting Autophagy Cascade Against Coronavirus Infection.
    Maity S, Saha A. · · 2021 · cited 28× · PMID 34054782 · DOI 10.3389/fmicb.2021.675419
  8. Approaching coronavirus disease 2019: Mechanisms of action of repurposed drugs with potential activity against SARS-CoV-2.
    Lisi L, Lacal PM, Barbaccia ML, Graziani G. · · 2020 · cited 20× · PMID 32710969 · DOI 10.1016/j.bcp.2020.114169

Verify or expand the search:

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04358081.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing