Respiratory Tract Infection ViralPhase 3NCT05026801
Azithromycin Plus Hydroxychloroquine for COVID-19 Infection
A Phase 3 study testing Azithromycin plus hydroxychloroquine in people with Respiratory Tract Infection Viral, run by Iterum Therapeutics, International Limited at 1 site in United States.
Trial summary
This is a randomized, double-blinded, Phase 3, multi-center trial of the clinical and microbiologic response of patients with a respiratory tract infection (RTI) due to coronavirus treated with a combination of azithromycin and hydroxychloroquine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiratory Tract Infection Viral
- What is being tested?
- Azithromycin plus hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Feb 2021to 26 Aug 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥18 years of age
- History of a respiratory tract infection (RTI) for more than one but less than six days including two or more of the following signs and symptoms of an RTI:
- Fever (T ≥ 38.0 C, 100.5 F), cough, sputum production, arthralgia/myalgia, anosmia/ageusia or difficulty breathing.
- A nasal or throat swab or nasal wash positive by PCR for SARS-CoV-2.
- Has given written informed consent to participate in the study. Due to the public health issues related to this viral infection, witnessed informed consent may be obtained remotely.
Who cannot join
- Patients likely, in the opinion of the investigator, to require hospitalization within 48 hours of randomization into the study.
- Concurrent use of non-study antibacterial drug therapy that would have a potential effect on outcome evaluations in patients with an RTI
- Concurrent use of any other medications for the purpose of treating a viral infection such as influenza antivirals
- Inability to swallow oral medication in tablet form
- Patient has severe chronic kidney disease, or is receiving hemodialysis, or peritoneal dialysis or had a renal transplant
- Patient is known to have severe neutropenia
Show all 11Show fewer
- Patients with a known prolongation of the QT interval or are taking medications which could prolong the QT interval
- Patient is known to be pregnant
- Patients with a known history of myasthenia gravis
- Patients with a history of allergy to azithromycin, hydroxychloroquine or chloroquine
- Patient is considered unlikely to survive the study period or has a rapidly progressive or terminal illness, including septic shock, associated with a high risk of mortality
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-blinded Phase 3 Multi-center Study of the Clinical and Microbiologic Efficacy of a Combination of Azithromycin and Hydroxychloroquine for Treatment of COVID-19 Infection
This is a randomized, double-blinded, Phase 3, multi-center trial of the clinical and microbiologic response of patients with a respiratory tract infection (RTI) due to coronavirus treated with a combination of azithromycin and hydroxychloroquine.
Approximately 200 patients with symptoms of an RTI who test positive for SARS-CoV-2 by polymerase chain reaction (PCR) will receive a combination of azithromycin 500 mg and hydroxychloroquine 600 mg or matching placebos for six consecutive days. There will be two treatment regimens into which patients are randomized so that all patients will receive some active therapy.
Read the detailed description
As of March 22, 2020, a total of 311,988 people worldwide have been diagnosed with a respiratory infection caused by SARS-CoV-2 of whom 13,407 have died. In the United States 26,747 patients have tested positive of whom 340 have died. There is at present no established therapy for this infection. After the SARS epidemic in 2002, investigations identified chloroquine as a possible inhibitor of replication of this coronavirus. When the SARS-CoV-2 epidemic started in December of 2019, clinicians began to use chloroquine in an attempt to control the infection in newly diagnosed patients. Investigators from China reported chloroquine phosphate has apparent efficacy in treatment of pneumonia due to SARS-CoV-2. Following this report, investigators in France initiated an open label study of hydroxychloroquine, with the addition of azithromycin, in a small number of subjects with SARS-CoV-2 infection. Relative to no treatment the investigators identified a significant reduction in viral isolation by PCR in the nasal swabs of treated patients, with an additional effect seen when patients were also given azithromycin. Azithromycin, like chloroquine, is a weak base that concentrates in endosomes and lysosomes and raises the pH in those vesicles. It is possible that azithromycin and chloroquine's effect on endosomal processing reduces the inflammatory response by affecting TLR4 signaling through the endosomes.
- Conditions
- Respiratory Tract Infection Viral
- Being tested
- Azithromycin plus hydroxychloroquine
- Keywords
- Coronavirus
- Medical subject headings
- Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azithromycin plus hydroxychloroquineDrug
Also called Placebo
All patients will receive active comparator. One group will receive placebo on D1-3 followed by active comparator D4-9, while the other group will receive active comparator D1-6 followed by placebo D7-9.
| Study group | Role | What they receive |
|---|---|---|
| Azithromycin plus hydroxychloroquine | Active comparator | Azithromycin 500 mg plus hydroxychloroquine 600 mg by mouth daily for six consecutive days Receives: Drug: Azithromycin plus hydroxychloroquine |
| Placebo | Placebo comparator | Placebo Receives: Drug: Azithromycin plus hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Microbiologic response
Presence or absence of SARS-CoV-2 by PCR on nasopharyngeal specimen
Measured: Day 3 (+/- 1 day)
Secondary outcomes (1)
Combined clinical and microbiologic response
Presence or absence of SARS-CoV-2 by PCR on nasopharyngeal specimen and improvement in at least two of the signs and symptoms of RTI
Measured: Day 3 (+/- 1 day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2021
- Study start8 Feb 2021
- Primary completion26 Aug 2021
- Study completion26 Aug 2021
Why it stopped: Inadequate support to carry out study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiratory Tract Infection ViralStudies of the same condition, open and under way.
- 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
- Model description
- Approximately 200 patients with symptoms of a RTI who test positive for SARS-CoV-2 by polymerase chain reaction (PCR) will receive a combination of azithromycin 500 mg and chloroquine 500 mg or matching placebos for six consecutive days. There will be two treatment regimens into which patients are randomized so that all patients will receive some active therapy. A sequential probability ratio test will be employed in which comparisons between each regimen will be made with every Day 3 PCR endpoint; if the p value crosses a p=0.001 threshold for any pairwise comparison, the less efficacious arm will be closed to further enrollment and superiority will be declared.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Iterum Therapeutics, International Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Waterbury Hospital
- Responsible party
- Sponsor
- Investigators
- Michael Dunne, MD, Principal investigator, Iterum Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05026801
- Sponsor's protocol ID
- IT005-501
- Status last verified
- Oct 2021
- First submitted
- 8 Feb 2021
- Last updated
- 28 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified individual participant data for all primary and secondary outcome measures will be made available.
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blinded Phase 3 Multi-center Study of the Clinical and Microbiologic Efficacy of a Combination of Azithromycin and Hydroxychloroquine for Treatment of COVID-19 Infection
- ClinicalTrials.gov ID
- NCT05026801
- Acronym / sponsor ID
- IT005-501
- Conditions
- Respiratory Tract Infection Viral
- Keywords
- Coronavirus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Inadequate support to carry out study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Iterum Therapeutics, International LimitedIndustry (pharma, biotech, devices)
- Collaborators
- Waterbury Hospital
- Study start
- 8 Feb 2021 (actual)
- Primary completion
- 26 Aug 2021 (actual)
- Study completion
- 26 Aug 2021 (actual)
- First posted
- 30 Aug 2021 (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.
This is a randomized, double-blinded, Phase 3, multi-center trial of the clinical and microbiologic response of patients with a respiratory tract infection (RTI) due to coronavirus treated with a combination of azithromycin and hydroxychloroquine.
Approximately 200 patients with symptoms of an RTI who test positive for SARS-CoV-2 by polymerase chain reaction (PCR) will receive a combination of azithromycin 500 mg and hydroxychloroquine 600 mg or matching placebos for six consecutive days. There will be two treatment regimens into which patients are randomized so that all patients will receive some active therapy.
Detailed description
As of March 22, 2020, a total of 311,988 people worldwide have been diagnosed with a respiratory infection caused by SARS-CoV-2 of whom 13,407 have died. In the United States 26,747 patients have tested positive of whom 340 have died. There is at present no established therapy for this infection. After the SARS epidemic in 2002, investigations identified chloroquine as a possible inhibitor of replication of this coronavirus. When the SARS-CoV-2 epidemic started in December of 2019, clinicians began to use chloroquine in an attempt to control the infection in newly diagnosed patients. Investigators from China reported chloroquine phosphate has apparent efficacy in treatment of pneumonia due to SARS-CoV-2. Following this report, investigators in France initiated an open label study of hydroxychloroquine, with the addition of azithromycin, in a small number of subjects with SARS-CoV-2 infection. Relative to no treatment the investigators identified a significant reduction in viral isolation by PCR in the nasal swabs of treated patients, with an additional effect seen when patients were also given azithromycin. Azithromycin, like chloroquine, is a weak base that concentrates in endosomes and lysosomes and raises the pH in those vesicles. It is possible that azithromycin and chloroquine's effect on endosomal processing reduces the inflammatory response by affecting TLR4 signaling through the endosomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Approximately 200 patients with symptoms of a RTI who test positive for SARS-CoV-2 by polymerase chain reaction (PCR) will receive a combination of azithromycin 500 mg and chloroquine 500 mg or matching placebos for six consecutive days. There will be two treatment regimens into which patients are randomized so that all patients will receive some active therapy. A sequential probability ratio test will be employed in which comparisons between each regimen will be made with every Day 3 PCR endpoint; if the p value crosses a p=0.001 threshold for any pairwise comparison, the less efficacious arm will be closed to further enrollment and superiority will be declared.
| Arm | Type | Receives |
|---|---|---|
| Azithromycin plus hydroxychloroquine | Active comparator | Drug: Azithromycin plus hydroxychloroquineAzithromycin 500 mg plus hydroxychloroquine 600 mg by mouth daily for six consecutive days |
| Placebo | Placebo comparator | Drug: Azithromycin plus hydroxychloroquinePlacebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults ≥18 years of age
- History of a respiratory tract infection (RTI) for more than one but less than six days including two or more of the following signs and symptoms of an RTI:
- A nasal or throat swab or nasal wash positive by PCR for SARS-CoV-2.
- Has given written informed consent to participate in the study. Due to the public health issues related to this viral infection, witnessed informed consent may be obtained remotely.
Key exclusion criteria (11 listed)
- Patients likely, in the opinion of the investigator, to require hospitalization within 48 hours of randomization into the study.
- Concurrent use of non-study antibacterial drug therapy that would have a potential effect on outcome evaluations in patients with an RTI
- Concurrent use of any other medications for the purpose of treating a viral infection such as influenza antivirals
- Inability to swallow oral medication in tablet form
- Patient has severe chronic kidney disease, or is receiving hemodialysis, or peritoneal dialysis or had a renal transplant
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 |
|---|---|---|
| Azithromycin plus hydroxychloroquineAlso: PlaceboAll patients will receive active comparator. One group will receive placebo on D1-3 followed by active comparator D4-9, while the other group will receive active comparator D1-6 followed by placebo D7-9. | Drug | Azithromycin plus hydroxychloroquine, Placebo |
Primary outcome
Microbiologic response
Time frame: Day 3 (+/- 1 day)
Presence or absence of SARS-CoV-2 by PCR on nasopharyngeal specimen
1 secondary outcome
Combined clinical and microbiologic response
Time frame: Day 3 (+/- 1 day)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2021.
- Individual participant dataSharing planned: Yes. Deidentified individual participant data for all primary and secondary outcome measures will be made available.
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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.
Michael Dunne, MD principal investigator
Iterum Therapeutics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Azithromycin plus hydroxychloroquine in people with Respiratory Tract Infection Viral, run by Iterum Therapeutics, International Limited at 1 site in United States.
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 11 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: withdrawn, as of the sponsor's last update on 28 Oct 2021. 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 United States. 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 withdrawn before enrolling participants, so there are no results.
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?
Microbiologic response (time frame: Day 3 (+/- 1 day)). 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 28 Oct 2021.