Hydroxychloroquine, Oseltamivir and Azithromycin for the Treatment of COVID-19 Infection: An RCT (PROTECT)

• ClinicalTrials.gov Identifier: NCT04338698
• Recruitment Status: Completed
• First Posted: April 8, 2020
• Last Update Posted: February 10, 2022
• Sponsor: Shehnoor Azhar
• Information provided by (Responsible Party): Shehnoor Azhar, University of Health Sciences Lahore

Study Description

Brief Summary:

To evaluate the effectiveness of Hydroxychloroquine Sulfate (200 mg orally 8hr thrice a day for 5 days) vs oseltamivir (75 mg orally twice a day for 5 days) vs Azithromycin (500 mg orally daily on day 1, followed by 250 mg orally twice a day on days 2-5) alone and in combination (in all seven groups), in clearing the coronavirus nucleic acid from throat and nasal swab and in bringing about clinical improvement on day 7 of follow-up (primary outcomes).

Condition or disease	Intervention/treatment	Phase
COVID 19	Drug: Hydroxychloroquine; Drug: Oseltamivir; Drug: Azithromycin	Phase 3

Detailed Description:

A scientific taskforce notified by the Ministry of Science and Technology of the Government of Pakistan will oversee a comprehensive cohort study. Within this cohort, a multicenter, adaptive, randomized controlled trial will evaluate, among eligible SARS-Cov-2 (COVID-19) infected patients receiving standard supportive care who consent to randomization following a new diagnosis in Pakistan, if Hydroxychloroquine Sulfate alone (control intervention) vs a series of alternatives (comparator interventions) including Oseltamivir and Azithromycin alone and in combination with Hydroxychloroquine Sulfate is effective in clearing the coronavirus and improving the clinical course of the disease. Those not consenting to randomization will be followed up for outcomes of SARS-Cov-2 infection with supportive care only. Findings of this study are expected to inform clinical care and public health protocols and policies for management of SARS-Cov-2.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 550 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Adaptive design (sample size given below is indicative)
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Pakistan Randomized and Observational Trial to Evaluate Coronavirus Treatment
• Actual Study Start Date: April 22, 2020
• Actual Primary Completion Date: November 15, 2020
• Actual Study Completion Date: November 22, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Control Intervention; Hydroxychloroquine	Drug: Hydroxychloroquine; Hydroxychloroquine Sulfate (200 mg orally thrice a day for 5 days)
Experimental: Comparator 1; Azithromycin	Drug: Azithromycin; Azithromycin (500 mg orally once a day on day 1, followed by 250 mg orally daily on days 2-5)
Experimental: Comparator 2; Oseltamivir	Drug: Oseltamivir; Oseltamivir (75 mg orally twice a day for 5 days)
Experimental: Comparator 3; Hydroxychloroquine + Azithromycin	Drug: Hydroxychloroquine; Hydroxychloroquine Sulfate (200 mg orally thrice a day for 5 days); Drug: Azithromycin; Azithromycin (500 mg orally once a day on day 1, followed by 250 mg orally daily on days 2-5)
Experimental: Comparator 4; Hydroxychloroquine + Oseltamivir	Drug: Hydroxychloroquine; Hydroxychloroquine Sulfate (200 mg orally thrice a day for 5 days); Drug: Oseltamivir; Oseltamivir (75 mg orally twice a day for 5 days)
Experimental: Comparator 5; Oseltamivir + Azithromycin	Drug: Oseltamivir; Oseltamivir (75 mg orally twice a day for 5 days); Drug: Azithromycin; Azithromycin (500 mg orally once a day on day 1, followed by 250 mg orally daily on days 2-5)
Experimental: Comparator 6; Hydroxyquinine + Oseltamivir + Azithromycin	Drug: Hydroxychloroquine; Hydroxychloroquine Sulfate (200 mg orally thrice a day for 5 days); Drug: Oseltamivir; Oseltamivir (75 mg orally twice a day for 5 days); Drug: Azithromycin; Azithromycin (500 mg orally once a day on day 1, followed by 250 mg orally daily on days 2-5)
No Intervention: Observational Cohort; Non-consenting to randomization

Outcome Measures

Primary Outcome Measures :

1. Laboratory Result [ Time Frame: Day 07 on follow-up ]
   The laboratory-based primary outcome will be turning test negative for COVID-19 on RT-qPCR calculated as viral load of < 150 i.u
2. Clinical Outcome [ Time Frame: Day 07 on follow-up ]

   The clinical primary outcome will be improvement of two points on a seven-category ordinal scale shown below:

   1. Not hospitalized, able to resume normal activities
   2. Not hospitalized, but unable to resume normal activities
   3. Hospitalization, not requiring supplemental oxygen
   4. Hospitalization, requiring supplemental oxygen
   5. Hospitalization, requiring noninvasive mechanical ventilation
   6. Hospitalization, requiring invasive mechanical ventilation
   7. Death

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:

1. Confirmed SARS-CoV-2 (COVID-19) infection by a positive test result
2. Either gender
3. Symptomatic for example fever, dry Cough, difficulty to breathe

Exclusion Criteria:

1. Confirmed absence of SARS-CoV-2 (COVID-19) infection by a negative test result
2. Have chronic conditions such as heart disease, liver and kidney failure
3. Pregnant or currently lactating
4. Immunocompromise and/or systemic disease(s)
5. On other antiviral drugs
6. History of allergy to any of the drugs to be administered in this study

Contacts and Locations

Locations

Pakistan

Faislabad Medical University

Faisalābad, Pakistan

Gujranwala Medical College

Gujrānwāla, Pakistan

Nawaz Sharif Medical College

Gujrāt, Pakistan

Szabmu-Pims

Islamabad, Pakistan

Akram Medical Complex

Lahore, Pakistan

Fatima Jinnah Medical University

Lahore, Pakistan

King Edward Medical University-Mayo Hospital

Lahore, Pakistan

Lahore General Hospital

Lahore, Pakistan

Khyber Teaching Hospital

Peshawar, Pakistan

Rawalpindi Medical University

Rawalpindi, Pakistan

Sargodha Medical College

Sargodha, Pakistan

Sponsors and Collaborators

Shehnoor Azhar

Investigators

• Principal Investigator: Javed Akram, FRCP; University of Health Sciences Lahore

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Akram J, Azhar S, Shahzad M, Latif W, Khan KS. Pakistan Randomized and Observational Trial to Evaluate Coronavirus Treatment (PROTECT) of Hydroxychloroquine, Oseltamivir and Azithromycin to treat newly diagnosed patients with COVID-19 infection who have no comorbidities like diabetes mellitus: A structured summary of a study protocol for a randomized controlled trial. Trials. 2020 Aug 8;21(1):702. doi: 10.1186/s13063-020-04616-4. Erratum in: Trials. 2020 Aug 22;21(1):733. Trials. 2022 Feb 15;23(1):150.

• Responsible Party: Shehnoor Azhar, Study Coordinator, University of Health Sciences Lahore
• ClinicalTrials.gov Identifier: NCT04338698
• Other Study ID Numbers: 12(06)/2016-Coord
• First Posted: April 8, 2020
• Last Update Posted: February 10, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: On completion of study, investigators are open to participation in planned IPD projects with a prospective registration, subject to appropriate approvals

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

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Azithromycin; Hydroxychloroquine; Oseltamivir; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antiviral Agents