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Azithromycin Plus Hydroxychloroquine for COVID-19 Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05026801
Recruitment Status : Withdrawn (Inadequate support to carry out study)
First Posted : August 30, 2021
Last Update Posted : October 28, 2021
Sponsor:
Collaborator:
Waterbury Hospital
Information provided by (Responsible Party):
Iterum Therapeutics, International Limited

Brief 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.

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.


Condition or disease Intervention/treatment Phase
Respiratory Tract Infection Viral Drug: Azithromycin plus hydroxychloroquine Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator)
Masking Description: Double-blinded
Primary Purpose: Treatment
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
Actual Study Start Date : February 8, 2021
Actual Primary Completion Date : August 26, 2021
Actual Study Completion Date : August 26, 2021


Arm Intervention/treatment
Active Comparator: Azithromycin plus hydroxychloroquine
Azithromycin 500 mg plus hydroxychloroquine 600 mg by mouth daily for six consecutive days
Drug: Azithromycin plus hydroxychloroquine
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.
Other Name: Placebo

Placebo Comparator: Placebo
Placebo
Drug: Azithromycin plus hydroxychloroquine
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.
Other Name: Placebo




Primary Outcome Measures :
  1. Microbiologic response [ Time Frame: Day 3 (+/- 1 day) ]
    Presence or absence of SARS-CoV-2 by PCR on nasopharyngeal specimen


Secondary Outcome Measures :
  1. Combined clinical and microbiologic response [ Time Frame: Day 3 (+/- 1 day) ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adults ≥18 years of age
  2. 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.

  3. A nasal or throat swab or nasal wash positive by PCR for SARS-CoV-2.
  4. 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.

Exclusion Criteria:

Exclusion Criteria:

  1. Patients likely, in the opinion of the investigator, to require hospitalization within 48 hours of randomization into the study.
  2. Concurrent use of non-study antibacterial drug therapy that would have a potential effect on outcome evaluations in patients with an RTI
  3. Concurrent use of any other medications for the purpose of treating a viral infection such as influenza antivirals
  4. Inability to swallow oral medication in tablet form
  5. Patient has severe chronic kidney disease, or is receiving hemodialysis, or peritoneal dialysis or had a renal transplant
  6. Patient is known to have severe neutropenia
  7. Patients with a known prolongation of the QT interval or are taking medications which could prolong the QT interval
  8. Patient is known to be pregnant
  9. Patients with a known history of myasthenia gravis
  10. Patients with a history of allergy to azithromycin, hydroxychloroquine or chloroquine
  11. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05026801


Locations
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United States, Connecticut
Waterbury Hospial
Waterbury, Connecticut, United States, 06708
Sponsors and Collaborators
Iterum Therapeutics, International Limited
Waterbury Hospital
Investigators
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Principal Investigator: Michael Dunne, MD Iterum Therapeutics
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Responsible Party: Iterum Therapeutics, International Limited
ClinicalTrials.gov Identifier: NCT05026801    
Other Study ID Numbers: IT005-501
First Posted: August 30, 2021    Key Record Dates
Last Update Posted: October 28, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Deidentified individual participant data for all primary and secondary outcome measures will be made available.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Data will be available within 30 days of study completion.
Access Criteria: Data access requests will be reviewed on a case by case basis. Requestors will be required to sign a Data Access Agreement.
URL: http://www.iterumtx.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Iterum Therapeutics, International Limited:
Coronavirus
Additional relevant MeSH terms:
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Infections
Communicable Diseases
Respiratory Tract Infections
Virus Diseases
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Azithromycin
Hydroxychloroquine
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents