COVID-19Phase 2COMIHYNCT04340544
Hydroxychloroquine for the Treatment of Mild COVID-19 Disease
A Phase 2 study testing Hydroxychloroquine in people with COVID-19, run by University Hospital Tuebingen at 1 site in Germany.
Trial summary
The current outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a global health emergency with a case fatality rate so far approximately 4% and a growing number of confirmed cases (>57.000) in Germany. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- COVID-19
- What is being tested?
- Hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteGermany
- Study dates
- 22 Apr 2020to 12 Oct 2020
- Phase
- Phase 2
- 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
- Must be ≥18 years at the time of signing the informed consent
- Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures
- Able to adhere to the study visit schedule and other protocol requirements
- Mild COVID-19 with outpatient management as decided by the treating physician
- Early warning score for 2019-nCoV infected patients ≤ 5
- Females of childbearing potential (FCBP1) must agree
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- to utilize two reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact for at least 28 days before starting study drug, while participating in the study (including dose interruptions), and for at least 28 days after study treatment discontinuation and must agree to regular pregnancy testing during this timeframe
- to abstain from breastfeeding during study participation and 28 days after study drug discontinuation
- All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment
- All subjects must agree not to share medication
Who cannot join
- Requirement for oxygen administration
- Shortness of breath in resting position
- Creatinin > 2.0 mg/dl
- Women during pregnancy and lactation
- Participation in other clinical trials or observation period of competing trials
- Active or clinically significant cardiac disease including congestive heart failure (New York Heart Association Class III or higher)
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- History or current evidence of clinically significant cardiac arrhythmia except atrial fibrillation or paroxysmal supraventricular tachycardia
- Use of concomitant medications that prolong the QT/QTc interval
- Physician decision that involvement in the study is not in the patient´s best interest
Trial locations and contacts
1 site in 1 country.
About this study
The current outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a global health emergency with a case fatality rate so far approximately 4% and a growing number of confirmed cases (>57.000) 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 [1] replication and anecdotal reports from Chinese COVID-19 patients [2, 3] suggest that chloroquine is a good candidate for treatment. No data have been published and reported evidence is based on non-controlled use of hydroxychloroquine.
The aim of this placebo-controlled trial is to assess the effect of hydroxychloroquine on duration of symptoms in mild COVID-19 patients and time of virus shedding as an important tool to reduce the risk of further community transmissions. This data will inform practice for the design of larger trials on clinical efficacy of hydroxychloroquine in the treatment and post- and preexposure prophylaxis of COVID-19 and as a tool for reduction of community transmission.
Read the detailed description
The study is a double-blinded randomized placebo controlled multicentric trial. The trial is expected to be conducted from April to January 2021. The duration for each individual subject includes 7 days study treatment and 21±2 days of follow-up after the last study treatment administration time. Adult male and female patients with positive COVID-19 diagnosis and fulfilling the outlined eligibility criteria will be enrolled into the study. Trial population will consist of both genders. Gender distribution in the trial is supposed to reflect the distribution in the real patient's population, there will be no prior defined quantitative ratio between females and males.
All consenting and eligible adult patients with virologically confirmed COVID-19 will be recruited and randomly and double-blindly (patient and investigators) allocated in a 1:1 ratio to either IMP or placebo. Each patient will be given a first dose of 600mg IMP (hydroxychloroquine or placebo) at the day of inclusion at the study site. This amount corresponds to 3 capsules. From the 2nd day on, each patient will take 600mg once a day until day 7 (6 more doses of 600mg) at home and will document it in an online form or, when not possible, in a diary.
IMP will be given to the patients orally. To mask the IMP versus placebo the original tables will be encapsulated in a film coated tablet. After this step IMP and placebo will not be distinguishable. Only the pharmacy and an independent party are aware of group allocation.
Treatment phase:
Day 1:
After randomization and treatment allocation medical history, concomitant as well as previous (up to 2 weeks) medication and baseline characteristics of the patients will be captured and a physical examination will be performed. The patients will receive the full amount of study medication (drug or placebo) from a trained study nurse together with a diary. They will be instructed how and when to fill in the diary concerning drug intake, clinical signs and symptoms and, if applicable, any adverse events and changes in concomitant medication. The first assessment of clinical signs and symptoms and a throat swab including blood sample collection will be done under supervision of a study nurse. The patients will then take the first dose of the allocated treatment and document the intake in the diary. This will also take place under the supervision of a study nurse. Patients will then be discharged to home isolation.
Day 2 to Day 7:
On each of the following 6 days during home isolation the patients will take the study medication and document the intake and the clinical signs and symptoms in their online or paper diary. In case of any adverse events or changes in concomitant medication, the patients will document this in their diary as well. The patients will be asked to contact the investigator in case their clinical condition is getting worse. Home visits will be performed in case of clinically significant symptoms.
Day 8 to Day 13:
On each day, the patients are in home isolation and document the clinical signs and symptoms in their diary. In case of any adverse events or changes in concomitant medication, the patients will document this in their diary as well. The patients will be asked to contact the investigator in case their clinical condition is getting worse. As before, home visits will be performed when indicated.
Day 14±1:
Patients will go to the study site and bring their diary and any unused study medication (if applicable). Physical examination will be performed. The patients will document their clinical signs and symptoms, a throat swab and a blood sample will be taken under the supervision of a study nurse. They will be motivated to continue their diary for the follow-up phase with instruction how to use it.
Day 15 to Day 27:
On each day, the patients will document the clinical signs and symptoms in their diary. In case of any adverse events or changes in concomitant medication, the patients will document this in their diary as well. The patients will be asked to contact the investigator in case their clinical condition is getting worse.
Day 28±2:
Patients will go to the study site and bring their follow-up diary. Physical examination will be performed. The patients will document their clinical signs and symptoms. Blood and throat swab will be taken in a subset of patients under the supervision of a study nurse. Their study participation will then be terminated.
- Conditions
- COVID-19
- Being tested
- Hydroxychloroquine, 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 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 | Experimental | Hydroxychloroquine 600mg daily for 7 days Receives: Drug: Hydroxychloroquine |
| Placebo | Placebo comparator | Equivalent number of placebo capsules Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in time to resolution of clinical signs and symptoms of mild COVID-19 treated with hydroxychloroquine or placebo as assessed by daily self-assessment
Measured: 28±2 days
Secondary outcomes (2)
Difference between hydroxychloroquine- and placebotreated patients on an ordinal outcome scale until Day 28 (death, admission to intensive care, hospitalization, continuing disease, recovered)
Measured: 28±2 days
All-cause mortality within 28 days
Measured: 28±2 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2020
- Study start22 Apr 2020
- Primary completion12 Oct 2020
- Study completion12 Oct 2020
Why it stopped: It appeared to be impossible for the study centres to recruit the targeted number of patients, due to reduced incidence and reduced acceptance to IMP
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 17 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04340544
- Sponsor's protocol ID
- COMIHY
- Acronym
- COMIHY
- Status last verified
- Apr 2020
- First submitted
- 3 Apr 2020
- Last updated
- 2 Nov 2020
- 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 2 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydroxychloroquine for the Treatment of Mild COVID-19 Disease
- ClinicalTrials.gov ID
- NCT04340544
- Acronym / sponsor ID
- COMIHY / COMIHY
- Conditions
- COVID-19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: It appeared to be impossible for the study centres to recruit the targeted number of patients, due to reduced incidence and reduced acceptance to IMP
- Enrolment
- 17 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
- 22 Apr 2020 (actual)
- Primary completion
- 12 Oct 2020 (actual)
- Study completion
- 12 Oct 2020 (actual)
- First posted
- 9 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 coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a global health emergency with a case fatality rate so far approximately 4% and a growing number of confirmed cases (>57.000) 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 [1] replication and anecdotal reports from Chinese COVID-19 patients [2, 3] suggest that chloroquine is a good candidate for treatment. No data have been published and reported evidence is based on non-controlled use of hydroxychloroquine.
The aim of this placebo-controlled trial is to assess the effect of hydroxychloroquine on duration of symptoms in mild COVID-19 patients and time of virus shedding as an important tool to reduce the risk of further community transmissions. This data will inform practice for the design of larger trials on clinical efficacy of hydroxychloroquine in the treatment and post- and preexposure prophylaxis of COVID-19 and as a tool for reduction of community transmission.
Detailed description
The study is a double-blinded randomized placebo controlled multicentric trial. The trial is expected to be conducted from April to January 2021. The duration for each individual subject includes 7 days study treatment and 21±2 days of follow-up after the last study treatment administration time. Adult male and female patients with positive COVID-19 diagnosis and fulfilling the outlined eligibility criteria will be enrolled into the study. Trial population will consist of both genders. Gender distribution in the trial is supposed to reflect the distribution in the real patient's population, there will be no prior defined quantitative ratio between females and males.
All consenting and eligible adult patients with virologically confirmed COVID-19 will be recruited and randomly and double-blindly (patient and investigators) allocated in a 1:1 ratio to either IMP or placebo. Each patient will be given a first dose of 600mg IMP (hydroxychloroquine or placebo) at the day of inclusion at the study site. This amount corresponds to 3 capsules. From the 2nd day on, each patient will take 600mg once a day until day 7 (6 more doses of 600mg) at home and will document it in an online form or, when not possible, in a diary.
IMP will be given to the patients orally. To mask the IMP versus placebo the original tables will be encapsulated in a film coated tablet. After this step IMP and placebo will not be distinguishable. Only the pharmacy and an independent party are aware of group allocation.
Treatment phase:
Day 1:
After randomization and treatment allocation medical history, concomitant as well as previous (up to 2 weeks) medication and baseline characteristics of the patients will be captured and a physical examination will be performed. The patients will receive the full amount of study medication (drug or placebo) from a trained study nurse together with a diary. They will be instructed how and when to fill in the diary concerning drug intake, clinical signs and symptoms and, if applicable, any adverse events and changes in concomitant medication. The first assessment of clinical signs and symptoms and a throat swab including blood sample collection will be done under supervision of a study nurse. The patients will then take the first dose of the allocated treatment and document the intake in the diary. This will also take place under the supervision of a study nurse. Patients will then be discharged to home isolation.
Day 2 to Day 7:
On each of the following 6 days during home isolation the patients will take the study medication and document the intake and the clinical signs and symptoms in their online or paper diary. In case of any adverse events or changes in concomitant medication, the patients will document this in their diary as well. The patients will be asked to contact the investigator in case their clinical condition is getting worse. Home visits will be performed in case of clinically significant symptoms.
Day 8 to Day 13:
On each day, the patients are in home isolation and document the clinical signs and symptoms in their diary. In case of any adverse events or changes in concomitant medication, the patients will document this in their diary as well. The patients will be asked to contact the investigator in case their clinical condition is getting worse. As before, home visits will be performed when indicated.
Day 14±1:
Patients will go to the study site and bring their diary and any unused study medication (if applicable). Physical examination will be performed. The patients will document their clinical signs and symptoms, a throat swab and a blood sample will be taken under the supervision of a study nurse. They will be motivated to continue their diary for the follow-up phase with instruction how to use it.
Day 15 to Day 27:
On each day, the patients will document the clinical signs and symptoms in their diary. In case of any adverse events or changes in concomitant medication, the patients will document this in their diary as well. The patients will be asked to contact the investigator in case their clinical condition is getting worse.
Day 28±2:
Patients will go to the study site and bring their follow-up diary. Physical examination will be performed. The patients will document their clinical signs and symptoms. Blood and throat swab will be taken in a subset of patients under the supervision of a study nurse. Their study participation will then be terminated.
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 | Experimental | Drug: HydroxychloroquineHydroxychloroquine 600mg daily for 7 days |
| Placebo | Placebo comparator | Drug: PlaceboEquivalent number of placebo capsules |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Must be ≥18 years at the time of signing the informed consent
- Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures
- Able to adhere to the study visit schedule and other protocol requirements
- Mild COVID-19 with outpatient management as decided by the treating physician
- Early warning score for 2019-nCoV infected patients ≤ 5
Key exclusion criteria (9 listed)
- Requirement for oxygen administration
- Shortness of breath in resting position
- Creatinin > 2.0 mg/dl
- Women during pregnancy and lactation
- Participation in other clinical trials or observation period of competing trials
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 |
|---|---|---|
| HydroxychloroquineHydroxychloroquine 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 |
| PlaceboPlacebo capsules | Drug | Placebo |
Primary outcome
Difference in time to resolution of clinical signs and symptoms of mild COVID-19 treated with hydroxychloroquine or placebo as assessed by daily self-assessment
Time frame: 28±2 days
2 secondary outcomes
Difference between hydroxychloroquine- and placebotreated patients on an ordinal outcome scale until Day 28 (death, admission to intensive care, hospitalization, continuing disease, recovered)
Time frame: 28±2 days
All-cause mortality within 28 days
Time frame: 28±2 days
Results and safety
The study was stopped early (reason given: It appeared to be impossible for the study centres to recruit the targeted number of patients, due to reduced incidence and reduced acceptance to IMP). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2020.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hydroxychloroquine in people with COVID-19, run by University Hospital Tuebingen at 1 site 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 10 inclusion and 9 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 2 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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: It appeared to be impossible for the study centres to recruit the targeted number of patients, due to reduced incidence and reduced acceptance to 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?
Difference in time to resolution of clinical signs and symptoms of mild COVID-19 treated with hydroxychloroquine or placebo as assessed by daily self-assessment (time frame: 28±2 days). 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 2 Nov 2020.