COVID-19, Hydroxychloroquine SulfatePhase 3COV-HCQNCT04342221
Hydroxychloroquine for COVID-19
A Phase 3 study testing Hydroxychloroquine Sulfate in people with COVID-19, Hydroxychloroquine Sulfate, run by University Hospital Tuebingen at 8 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- COVID-19, Hydroxychloroquine Sulfate
- What is being tested?
- Hydroxychloroquine Sulfate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 8 sitesGermany
- Study dates
- 29 Mar 2020to 26 Feb 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Germany8 sites
Zollernalb Klinikum Balingen
Balingen, 72336
Klinikum Darmstadt
Darmstadt, 64283
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20359
Johannes Wesling Klinikum Minden
Minden, 32429
Klinikum am Steinenberg
Reutlingen, 72764
RoMed Klinikum Rosenheim
Rosenheim, 83022
Robert-Bosch-Krankenhaus
Stuttgart, 70376
Institute for Tropical Medicine
Tübingen, 72074
About this study
Official title: Randomized Controlled Trial of Hydroxychloroquine Versus Placebo for the Treatment of Adult Patients With Acute Coronavirus Disease 2019 - COVID-19
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.
Read the 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.
- Conditions
- COVID-19, Hydroxychloroquine Sulfate
- Being tested
- Hydroxychloroquine Sulfate, Placebo
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxychloroquine SulfateDrug
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.
PlaceboDrug
Placebo capsules
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Hydroxychloroquine Sulfate |
| Placebo | Placebo comparator | Equivalent number of placebo capsules at the day of inclusion (4 capsules) and the following days (3 capsules) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2020
- Study start29 Mar 2020
- Primary completion26 Feb 2021
- Study completion26 Feb 2021
Why it stopped: Reduced acceptance of IMP
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19, Hydroxychloroquine SulfateStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Collaborators
- Robert Bosch Medical Center, Universitätsklinikum Hamburg-Eppendorf, Bernhard Nocht Institute for Tropical Medicine
- Responsible party
- Sponsor
- Investigators
- Benjamin Mordmüller, Prof., Principal investigator, University Hospital Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04342221
- Sponsor's protocol ID
- COV-HCQ
- Other IDs
- 2020-001224-33
- Acronym
- COV-HCQ
- Status last verified
- Mar 2020
- First submitted
- 8 Apr 2020
- Last updated
- 3 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial of Hydroxychloroquine Versus Placebo for the Treatment of Adult Patients With Acute Coronavirus Disease 2019 - COVID-19
- ClinicalTrials.gov ID
- NCT04342221
- Acronym / sponsor ID
- COV-HCQ / COV-HCQ
- Conditions
- COVID-19, Hydroxychloroquine Sulfate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Reduced acceptance of IMP
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Collaborators
- Robert Bosch Medical Center, Universitätsklinikum Hamburg-Eppendorf, Bernhard Nocht Institute for Tropical Medicine
- Study start
- 29 Mar 2020 (actual)
- Primary completion
- 26 Feb 2021 (actual)
- Study completion
- 26 Feb 2021 (actual)
- First posted
- 10 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine Sulfate | Experimental | Drug: Hydroxychloroquine SulfateFirst 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). |
| Placebo | Placebo comparator | Drug: PlaceboEquivalent number of placebo capsules at the day of inclusion (4 capsules) and the following days (3 capsules) |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (14 listed)
- Respiratory rate >24/min
- Pregnancy (tested with a pregnancy test) or lactation
- Weight <50 kg
- Hemodynamic/rhythm instability
- Acute myocardial infarction Type 1
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxychloroquine SulfateHydroxychloroquine 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. | Drug | Hydroxychloroquine Sulfate |
| PlaceboPlacebo capsules | Drug | Placebo |
Primary outcome
Effect of HCQ on in vivo viral clearance
Time frame: 6 months
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.
Results and safety
The study was stopped early (reason given: Reduced acceptance of IMP). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2021.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benjamin Mordmüller, Prof. principal investigator
University Hospital Tuebingen
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydroxychloroquine Sulfate in people with COVID-19, Hydroxychloroquine Sulfate, run by University Hospital Tuebingen at 8 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Reduced acceptance of IMP). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of HCQ on in vivo viral clearance (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2021.