Azithromycin in Hospitalized COVID-19 Patients (AIC)

• ClinicalTrials.gov Identifier: NCT04359316
• Recruitment Status: Not yet recruiting
• First Posted: April 24, 2020
• Last Update Posted: April 24, 2020
• Sponsor: Shahid Beheshti University of Medical Sciences
• Information provided by (Responsible Party): Seyed Sina Naghibi Irvani, MD, MPH, MBA, Senior Researcher., Shahid Beheshti University of Medical Sciences

Study Description

Brief Summary:

The present study is a randomized, double-blind, controlled, clinical trial, with the approval of the ethics committee will be conducted on patients who have a positive test confirming COVID-19 in Shahid Modarres Medical Education Center and Hospital in Tehran. Patients will be randomly assigned to the two arms of the study and after completing the course of treatment and collecting and analyzing the necessary information from each patient, the results of the study will be published both on this site and in the form of an article in a reputable international journal.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Hydroxychloroquine; Drug: Azithromycin	Phase 4

Detailed Description:

Chloroquine has been a broadly-utilized anti-malaria agent which back in 2006, had been proved to be a powerful wide-spectrum antiviral. Moreover, Chloroquine has the characteristics of anti-inflammatory and immune-modulatory by inhibiting the production of TNF-α along with IL-6. In the first half of February, a study illustrated puissant inhibition of SARS-CoV-2 by Chloroquine, when taking two 500-mg tablets of it by mouth per day; similar to some clinical studies in China through this outbreak. According to the news briefing of a study, it was indicated that chloroquine phosphate actually outdo the control treatment in inhibition of pneumonia exacerbation, improving lung imaging findings, and curtailing the disease course. Another study evaluated the possible doses of CQ and HCQ to find the optimized dose in treatment of COVID-19. They revealed that while within in-vitro settings Hydroxychloroquine is more potent than chloroquine. As a conclusion, they suggested a 800 mg daily dose of hydroxychloroquine, followed by an overall maintenance dose of 400 mg per day divided in two separate doses, which was three-fold more potent compared to the 500 mg twice daily administration of chloroquine in 5 days. The new study published in 16th March, pointed out that hydroxychloroquine was notably effectual in eradicating SARS-CoV-2 from the nasopharynx. Currently the evidence is quite inconclusive about the effectiveness or comparative effectiveness of either HCQ or CQ. Moreover, CQ has recently become scarce and even unavailable for ordering due to a huge demand for it, all because of a significant interest gained as a potential medicinal alternative for the management of COVID-19. In spite of all, the primary experience in China and France is propitious for the potential role of chloroquine, or alternatively hydroxychloroquine, for managing COVID-19.

The reported clinical benefits of the combination of hydroxychloroquine and azithromycin for patients with COVID-19 come either from media reports or nonrandomized trials with small numbers of participants (<100 patients). The documented benefit of hydroxychloroquine with or without azithromycin is very limited, especially in severe disease. While these medications, individually or in combination, may prove efficacious, these benefits need to be established with randomized clinical trials prior to widespread adoption of these treatments.

The present study is a randomized, double-blind, controlled, clinical trial, with the approval of the ethics committee will be conducted on patients who have a positive test confirming COVID-19 in Shahid Modarres Medical Education Center and Hospital in Tehran. Patients will be randomly assigned to the two arms of the study and after completing the course of treatment and collecting and analyzing the necessary information from each patient, the results of the study will be published both on this site and in the form of an article in a reputable international journal.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: The present study is a randomized, double-blind, placebo-controlled, clinical trial, with the approval of the ethics committee will be conducted on patients who have a positive test confirming COVID-19 in Shahid Modarres Medical Education Center and Hospital in Tehran. Patients will be randomly assigned to the two arms of the study and after completing the course of treatment and collecting and analyzing the necessary information from each patient, the results of the study will be published both on this site and in the form of an article in a reputable international journal.
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Azithromycin Compared to the Base Therapeutic Regiment of Hydroxychloroquine in Moderate to Severe COVID-19: A Randomized, Controlled, Double-Blind, Clinical Trial
• Estimated Study Start Date: April 20, 2020
• Estimated Primary Completion Date: May 3, 2020
• Estimated Study Completion Date: May 5, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Azithromycin	Drug: Hydroxychloroquine; This Drug will be used in all arms as mandated by our governmental guidelines.; Drug: Azithromycin; This will be drug only used in the intervention arm of our study, designed mainly to assess the additional efficacy and safety of Azithromycin in COVID-19 patients.
Active Comparator: Hydroxychloroquine	Drug: Hydroxychloroquine; This Drug will be used in all arms as mandated by our governmental guidelines.

Outcome Measures

Primary Outcome Measures :

1. Time to clinical improvement [ Time Frame: From date of randomization until 14 days later. ]
   Improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever came first.

Secondary Outcome Measures :

1. Mortality [ Time Frame: From date of randomization until 14 days later. ]
   If the patient dies, we have reached an outcome.
2. SpO2 Improvement [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7 and 14. ]
   Pulse-oxymetry
3. Incidence of new mechanical ventilation use [ Time Frame: From date of randomization until 14 days later. ]
   Incidence of new mechanical ventilation use (Rate)
4. Duration of hospitalization [ Time Frame: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 14 days. ]
   Duration of hospitalization (Days)
5. Cumulative incidence of serious adverse events [ Time Frame: Days 1, 2, 3, 4, 5, 6, 7 and 14. ]
   With incidence of any serious adverse effects, the outcome has happened.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Age ≥ 18
• COVID-19 Confirmed Cases (Either RT-PCR or CT Scan Confirmed).
• Tympanic Temperature of ≥37.5 AND at least one of the following: Cough, Sputum production, nasal discharge, myalgia, headache or fatigue) on admission.
• Time of onset of the symptoms should be acute ( Days ≤ 10).
• SpO2 ≤ 93%
• Respiratory Rate ≥ 22

Exclusion Criteria:

• Refusal to participate expressed by patient or legally authorized representative if they are present.
• Patients with prolonged QT or PR intervals, Second or Third Degree heart block and Arrhythmias.
• Patients using drugs with potential interaction with Azithromycin or Hydroxychloroquine.
• Pregnant or lactating women.
• History of alcohol or drug addiction in the past 5 years.
• Blood ALT/AST levels > 5 times the upper limit of normal on laboratory results.

Contacts and Locations

Contacts

Contact: Seyed Sina Naghibi Irvani, MD, MPH, MBA; 09141182825; sina.irvani@gmail.com

Locations

Iran, Islamic Republic of

Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences and Health Services

Tehran, Iran, Islamic Republic of

Sponsors and Collaborators

Shahid Beheshti University of Medical Sciences

Investigators

• Study Chair: Mohammad Fathi, MD; Shahid Beheshti University of Medical Sciences
• Study Director: Sasan Tavana, MD; Shahid Beheshti University of Medical Sciences
• Principal Investigator: Nasser Malekpour Alamdari, MD; Shahid Beheshti University of Medical Sciences
• Principal Investigator: Mehran Lack, MD; Shahid Beheshti University of Medical Sciences
• Principal Investigator: Nader Markazi, MD; Shahid Beheshti University of Medical Sciences
• Principal Investigator: Sanaz Zargar Balaye Jam, MD; Shahid Beheshti University of Medical Sciences
• Principal Investigator: Seyed Sina Naghibi Irvani, MD, MPH, MBA; Shahid Beheshti University of Medical Sciences

More Information

• Responsible Party: Seyed Sina Naghibi Irvani, MD, MPH, MBA, Senior Researcher., Dr., Shahid Beheshti University of Medical Sciences
• ClinicalTrials.gov Identifier: NCT04359316
• Other Study ID Numbers: Azithromycin in COVID-19
• First Posted: April 24, 2020
• Last Update Posted: April 24, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: There is no further information.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Seyed Sina Naghibi Irvani, MD, MPH, MBA, Senior Researcher., Shahid Beheshti University of Medical Sciences:

COVID-19; SARS-CoV-2; Novel Coronavirus; Hydroxychloroquine; Chloroquine; Azithromycin

Additional relevant MeSH terms:

Azithromycin; Hydroxychloroquine; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents