Official Title
Randomized Controlled Trial of Hydroxychloroquine Versus Placebo for the Treatment of Adult Patients With Acute Coronavirus Disease 2019 - COVID-19
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.

Detailed Description

The study is a randomized placebo controlled multicentric Phase III trial. The duration of

the trial for each subject is expected to be 6 months. The duration for each individual

subject includes 7 days study treatment and 6 months follow-up time. Recruitment of subjects

will start in April 2020.



Adult male and female patients with positive COVID-19 diagnosis and fulfilling the below

outlined inclusion criteria will be enrolled into the study. Trial population will consist of

both genders.



Name of IMP: Hydroxychloroquine sulfate (HCQ); Quensyl. All consenting adult patients having

confirmed COVID-19 will be recruited and randomly and blindly allocated in a 1:1 ratio to

either IMP or placebo. Each patient will be given a first dose of 800 mg IMP or the

equivalent number of placebo capsules (4 capsules) at the day of inclusion (Day 1). From the

2nd day on, each patient will get 600 mg or the equivalent number if placebo capsules (3

capsules) once a day until day 7 (6 more does of 600 mg). The patient will be given the daily

dose of IMP at once for a total of 7 days.



Patients will be monitored on a daily basis until the endpoint (2 measurements of viral load

below 100 copies at least 24 hours apart) is reached. During admission visits will be

performed by the attending physician or study-nurse, after discharge visits will be performed

by qualified and trained study-personnel. Daily procedures will include a pharyngeal swab for

qPCR diagnostics (until primary endpoint is reached) and symptom assessment by questionnaire

and clinical examination. Blood draw for assessment of full blood count, routine clinical

chemistry and assessment of markers of inflammation, and immune response will be performed on

days 1, 2, 4, 7, 14, 30 and last follow up. ECG and measurement of cardiac enzymes will be

performed on a weekly basis or if clinically indicated to identify new onset arrhythmias.



The efficacy will be assessed by the daily throat swaps and directly followed measurement of

SARS-CoV-2-specific RNA copy number until the result of this test will be below the level of

detection during at least 2 consecutive visits (24h apart).



Safety will be assessed daily by the study physician until the endpoint is reached and at all

subsequent scheduled visits and contacts as well as at any unscheduled visit.

Recruiting
COVID-19, Hydroxychloroquine Sulfate

Drug: Hydroxychloroquine Sulfate
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

Drug: Placebo
Placebo capsules
Placebo

Eligibility Criteria

Inclusion Criteria: - 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

Exclusion Criteria: - Respiratory rate >24/min - Pregnancy (tested with a pregnancy test) or lactation - Weight

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years~Maximum: 99 Years
Countries
Germany
Contacts

Diane Egger-Adam, Dr.
+4970712982191
diane.egger-adam@uni-tuebingen.de

Thirumalaisamy Velavan, Prof.
+4970712985981
velavan@medizin.uni-tuebingen.de

Benjamin Mordmüller, Prof.
Principal Investigator
University Hospital Tübingen

University Hospital Tuebingen
Robert Bosch Medical Center
Universitätsklinikum Hamburg-Eppendorf
Bernhard Nocht Institute for Tropical Medicine
NCT Number
MeSH Terms
Hydroxychloroquine