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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Recruitment Status : Withdrawn (Inadequate support to carry out study)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

Tracking Information
First Submitted Date  ICMJE February 8, 2021
First Posted Date  ICMJE August 30, 2021
Last Update Posted Date October 28, 2021
Actual Study Start Date  ICMJE February 8, 2021
Actual Primary Completion Date August 26, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 26, 2021)
Microbiologic response [ Time Frame: Day 3 (+/- 1 day) ]
Presence or absence of SARS-CoV-2 by PCR on nasopharyngeal specimen
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 26, 2021)
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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Azithromycin Plus Hydroxychloroquine for COVID-19 Infection
Official Title  ICMJE 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
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.

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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE Respiratory Tract Infection Viral
Intervention  ICMJE 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
Study Arms  ICMJE
  • Active Comparator: Azithromycin plus hydroxychloroquine
    Azithromycin 500 mg plus hydroxychloroquine 600 mg by mouth daily for six consecutive days
    Intervention: Drug: Azithromycin plus hydroxychloroquine
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Drug: Azithromycin plus hydroxychloroquine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: August 26, 2021)
0
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 26, 2021
Actual Primary Completion Date August 26, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05026801
Other Study ID Numbers  ICMJE IT005-501
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: 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
Current Responsible Party Iterum Therapeutics, International Limited
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Iterum Therapeutics, International Limited
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Waterbury Hospital
Investigators  ICMJE
Principal Investigator: Michael Dunne, MD Iterum Therapeutics
PRS Account Iterum Therapeutics, International Limited
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP