Hydroxychloroquine for COVID-19

NCT04342221 | Terminated Phase 3 DMC

• 2 other identifiers: COV-HCQ2020-001224-33
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 8

Brief Summary

The current outbreak of COVID-19 caused by SARS-CoV-2 is a global health emergency with a case fatality rate so far approximately 4% and a growing number of confirmed cases (\>9500) in Germany. There is no data available on the efficacy of antiviral agents for the treatment of COVID-19. In vitro data show that hydroxychloroquine can inhibit SARS-CoV-2 replication and anecdotal reports from COVID-19 patients in China and France suggest that chloroquine or hydroxychloroquine is a good candidate for treatment. In the French study a favourable effect was seen when hydroxychloroquine was used together with azithromycin in a small series of COVID-19 patients. However, so far all published evidence is based on non-controlled use of hydroxychloroquine. We propose to conduct a placebo-controlled trial in COVID-19 patients with mild to moderate disease in Germany to assess virological efficacy, tolerability and safety of hydroxychloroquine in the treatment of COVID-19. The objective of this trial is to identify an effect of hydroxychloroquine on viral clearance in vivo. This data will inform practice for the design of larger trials on clinical efficacy of hydroxychloroquine in the treatment and post-exposure prophylaxis of COVID-19.

Conditions

COVID-19, Hydroxychloroquine Sulfate

Outcome Measures

Primary Outcomes (1)

• Effect of HCQ on in vivo viral clearance

  Viral clearance defined as time to sustained SARS-CoV-2-specific RNA copy number ≤100, measured by real time reverse-transcription polymerase chain reaction RT-PCR in throat swabs.

  6 months

Other Outcomes (7)

• In-hospital mortality

  60 days

• All-cause mortality

  60 days

• Proportion requiring non-invasive or invasive ventilation

  6 months

Study Arms (2)

Hydroxychloroquine Sulfate

EXPERIMENTAL

First dose: 800 mg. From 2nd day on, each patient will get 600 mg (3 capsules) once a day until day 7 (6 more does of 600 mg).

Drug: Hydroxychloroquine Sulfate

Placebo

PLACEBO COMPARATOR

Equivalent number of placebo capsules at the day of inclusion (4 capsules) and the following days (3 capsules)

Drug: Placebo

Interventions

Hydroxychloroquine Sulfate DRUG

Hydroxychloroquine Sulfate is an anti-malarial and anti-rheumatic drug and seems to be a potential candidate for the treatment of COVID-19 since it is able to block virus infection by increasing the endosomal pH, required for virus/cell fusion, it affects the activation of p38 mitogen-activated protein kinase (MAPK), involved in the replication of HCoV-229E and can interfere with the terminal glycosylation of ACE2, thus inhibiting SARS-CoV-2 infection.

Hydroxychloroquine Sulfate

Placebo DRUG

Placebo capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Age above 18 years
• Women of childbearing age only: Must agree to practice continuous effective contraception for the duration of the study (a method which results in a failure rate less than 1% per year)
• Disease severe enough to require hospitalization
• QTc interval lower than 450 msec

You may not qualify if:

• Respiratory rate \>24/min
• Pregnancy (tested with a pregnancy test) or lactation
• Weight \<50 kg
• Hemodynamic/rhythm instability
• Acute myocardial infarction Type 1
• Use of concomitant medications that prolong the QT/QTc interval.
• Any regular concomitant medication which is contraindicated in the use together with HCQ
• Hypersensitivity to Hydroxychloroquine, Chloroquine or other 4-Aminoquinolines
• Pre-existing retinopathy or maculopathy
• Known Glucose-6-phosphate dehydrogenase deficiency (haemolytic anaemia, Favism)
• Haematopoietic systems diseases
• Myasthenia gravis
• Any other significant disease, disorder or finding which, in the opinion of the investigator, may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data
• Additionally, clinical evaluation and laboratory values inform eligibility of the patient based on the judgement of the study team. These may include: total bilirubin, transaminase level, albumin concentration, haematological parameters, troponin and BNP levels, creatinine, creatinine kinase levels.

Sponsors & Collaborators

• University Hospital Tuebingen: lead
• Robert Bosch Medical Center: collaborator
• Universitätsklinikum Hamburg-Eppendorf: collaborator
• Bernhard Nocht Institute for Tropical Medicine: collaborator

Study Sites (8)

Zollernalb Klinikum Balingen

Balingen, 72336, Germany

Location

Klinikum Darmstadt

Darmstadt, 64283, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20359, Germany

Location

Johannes Wesling Klinikum Minden

Minden, 32429, Germany

Location

Klinikum am Steinenberg

Reutlingen, 72764, Germany

Location

RoMed Klinikum Rosenheim

Rosenheim, 83022, Germany

Location

Robert-Bosch-Krankenhaus

Stuttgart, 70376, Germany

Location

Institute for Tropical Medicine

Tübingen, 72074, Germany

Location

MeSH Terms

Conditions

COVID-19

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Benjamin Mordmüller, Prof.

  University Hospital Tübingen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2020
• First Posted: April 10, 2020
• Study Start: March 29, 2020
• Primary Completion: February 26, 2021
• Study Completion: February 26, 2021
• Last Updated: May 3, 2021

Record last verified: 2020-03

Locations

DE (8)