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Azithromycin Plus Hydroxychloroquine for COVID-19 Infection

Primary Purpose

Respiratory Tract Infection Viral

Status

Withdrawn

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Azithromycin plus hydroxychloroquine

About this trial

This is an interventional treatment trial for Respiratory Tract Infection Viral focused on measuring Coronavirus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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
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

Sites / Locations

Waterbury Hospial

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Azithromycin plus hydroxychloroquine

Placebo

Arm Description

Azithromycin 500 mg plus hydroxychloroquine 600 mg by mouth daily for six consecutive days

Placebo

Outcomes

Primary Outcome Measures

Microbiologic response

Presence or absence of SARS-CoV-2 by PCR on nasopharyngeal specimen

Secondary Outcome Measures

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

Full Information

NCT ID

NCT05026801

First Posted

February 8, 2021

Last Updated

October 26, 2021

Sponsor

Iterum Therapeutics, International Limited

Collaborators

Waterbury Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05026801

Brief Title

Azithromycin Plus Hydroxychloroquine for COVID-19 Infection

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Withdrawn

Why Stopped

Inadequate support to carry out study

Study Start Date

February 8, 2021 (Actual)

Primary Completion Date

August 26, 2021 (Actual)

Study Completion Date

August 26, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Iterum Therapeutics, International Limited

Collaborators

Waterbury Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Respiratory Tract Infection Viral

Keywords

Coronavirus

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

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

ParticipantCare ProviderInvestigator

Masking Description

Double-blinded

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Azithromycin plus hydroxychloroquine

Arm Type

Active Comparator

Arm Description

Azithromycin 500 mg plus hydroxychloroquine 600 mg by mouth daily for six consecutive days

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Azithromycin plus hydroxychloroquine

Other Intervention Name(s)

Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

Microbiologic response

Description

Presence or absence of SARS-CoV-2 by PCR on nasopharyngeal specimen

Time Frame

Day 3 (+/- 1 day)

Secondary Outcome Measure Information:

Title

Combined clinical and microbiologic response

Description

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

Time Frame

Day 3 (+/- 1 day)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: Exclusion Criteria: 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Dunne, MD

Organizational Affiliation

Iterum Therapeutics

Official's Role

Principal Investigator

Facility Information:

Facility Name

Waterbury Hospial

City

Waterbury

State/Province

Connecticut

ZIP/Postal Code

06708

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Deidentified individual participant data for all primary and secondary outcome measures will be made available.

IPD Sharing Time Frame

Data will be available within 30 days of study completion.

IPD Sharing Access Criteria

Data access requests will be reviewed on a case by case basis. Requestors will be required to sign a Data Access Agreement.

IPD Sharing URL

http://www.iterumtx.com

Learn more about this trial

Azithromycin Plus Hydroxychloroquine for COVID-19 Infection

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