COVID 19Phase 3PROTECTNCT04338698
Hydroxychloroquine, Oseltamivir and Azithromycin for the Treatment of COVID-19 Infection: An RCT
A Phase 3 study testing Hydroxychloroquine, Oseltamivir and Azithromycin in people with COVID 19, run by Shehnoor Azhar at 11 sites in Pakistan.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID 19
- What is being tested?
- Hydroxychloroquine, Oseltamivir and Azithromycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 550 participants
- Where
- 11 sitesPakistan
- Study dates
- 22 Apr 2020to 22 Nov 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed SARS-CoV-2 (COVID-19) infection by a positive test result
- Either gender
- Symptomatic for example fever, dry Cough, difficulty to breathe
Who cannot join
- Confirmed absence of SARS-CoV-2 (COVID-19) infection by a negative test result
- Have chronic conditions such as heart disease, liver and kidney failure
- Pregnant or currently lactating
- Immunocompromise and/or systemic disease(s)
- On other antiviral drugs
- History of allergy to any of the drugs to be administered in this study
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Pakistan11 sites
Gujranwala Medical College
Chak One Hundred Seventy-five Nine Left
Nawaz Sharif Medical College
Dhok Gujra
Faislabad Medical University
Faisalābad
Szabmu-Pims
Islamabad
Akram Medical Complex
Lahore
Fatima Jinnah Medical University
Lahore
King Edward Medical University-Mayo Hospital
Lahore
Lahore General Hospital
Lahore
Khyber Teaching Hospital
Peshawar
Rawalpindi Medical University
Rawalpindi
Sargodha Medical College
Sargodha
About this study
Official title: Pakistan Randomized and Observational Trial to Evaluate Coronavirus Treatment
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).
Read the 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.
- Conditions
- COVID 19
- Being tested
- Hydroxychloroquine, Oseltamivir, Azithromycin
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxychloroquine Sulfate (200 mg orally thrice a day for 5 days)
OseltamivirDrug
Oseltamivir (75 mg orally twice a day for 5 days)
AzithromycinDrug
Azithromycin (500 mg orally once a day on day 1, followed by 250 mg orally daily on days 2-5)
| Study group | Role | What they receive |
|---|---|---|
| Control Intervention | Active comparator | Hydroxychloroquine Receives: Drug: Hydroxychloroquine |
| Comparator 1 | Experimental | Azithromycin Receives: Drug: Azithromycin |
| Comparator 2 | Experimental | Oseltamivir Receives: Drug: Oseltamivir |
| Comparator 3 | Experimental | Hydroxychloroquine + Azithromycin Receives: Drug: Hydroxychloroquine; Drug: Azithromycin |
| Comparator 4 | Experimental | Hydroxychloroquine + Oseltamivir Receives: Drug: Hydroxychloroquine; Drug: Oseltamivir |
| Comparator 5 | Experimental | Oseltamivir + Azithromycin Receives: Drug: Oseltamivir; Drug: Azithromycin |
| Comparator 6 | Experimental | Hydroxyquinine + Oseltamivir + Azithromycin Receives: Drug: Hydroxychloroquine; Drug: Oseltamivir; Drug: Azithromycin |
| Observational Cohort | No intervention | Non-consenting to randomization |
What is being measured
The primary outcome is the main question the study is designed to answer.
Laboratory Result
The laboratory-based primary outcome will be turning test negative for COVID-19 on RT-qPCR calculated as viral load of < 150 i.u
Measured: Day 07 on follow-up
Clinical Outcome
The clinical primary outcome will be improvement of two points on a seven-category ordinal scale shown below:
- Not hospitalized, able to resume normal activities
- Not hospitalized, but unable to resume normal activities
- Hospitalization, not requiring supplemental oxygen
- Hospitalization, requiring supplemental oxygen
- Hospitalization, requiring noninvasive mechanical ventilation
- Hospitalization, requiring invasive mechanical ventilation
- Death
Measured: Day 07 on follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2020
- Study start22 Apr 2020
- Primary completion15 Nov 2020
- Study completion22 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for COVID 19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Adaptive design (sample size given below is indicative)
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 550 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shehnoor Azhar
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Shehnoor Azhar, University of Health Sciences Lahore
- Investigators
- Javed Akram, FRCP, Principal investigator, University of Health Sciences Lahore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04338698
- Sponsor's protocol ID
- 12(06)/2016-Coord
- Acronym
- PROTECT
- Status last verified
- Jan 2022
- First submitted
- 4 Apr 2020
- Last updated
- 10 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: On completion of study, investigators are open to participation in planned IPD projects with a prospective registration, subject to appropriate approvals
Publications
Azhar S, Akram J, Latif W, Ibanez NC, Mumtaz S, Rafi A, Aftab U, Iqtadar S, Shahzad M, Syed F, Zafar B, Fatima N, Afridi SS, Akram SJ, Chaudhary MA, Sadiq F, Goraya S, Hanif M, Ashraf V, Ashraf S, Akram H, Khaliq T. Effectiveness of early pharmaceutical interventions in symptomatic COVID-19 patients: A randomized clinical trial. Pak J Med Sci. 2024 May-Jun;40(5):800-810. doi: 10.12669/pjms.40.5.8757.
PubMed 38827854Azhar S, Akram J, Shahzad M, Latif W, Khan KS. Protocol of Pakistan randomized and observational trial to evaluate coronavirus treatment among newly diagnosed patients with COVID-19: Azithromycin, Oseltamivir, and Hydroxychloquine. Pak J Med Sci. 2022 May-Jun;38(5):1401-1408. doi: 10.12669/pjms.38.5.5512.
PubMed 35799756Akram 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.
PubMed 32771032
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pakistan Randomized and Observational Trial to Evaluate Coronavirus Treatment
- ClinicalTrials.gov ID
- NCT04338698
- Acronym / sponsor ID
- PROTECT / 12(06)/2016-Coord
- Conditions
- COVID 19
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 550 participants (actual)
- Lead sponsor
- Shehnoor AzharUniversity, hospital or other
- Study start
- 22 Apr 2020 (actual)
- Primary completion
- 15 Nov 2020 (actual)
- Study completion
- 22 Nov 2020 (actual)
- First posted
- 8 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 8
- Model description
- Adaptive design (sample size given below is indicative)
| Arm | Type | Receives |
|---|---|---|
| Control Intervention | Active comparator | Drug: HydroxychloroquineHydroxychloroquine |
| Comparator 1 | Experimental | Drug: AzithromycinAzithromycin |
| Comparator 2 | Experimental | Drug: OseltamivirOseltamivir |
| Comparator 3 | Experimental | Drug: Hydroxychloroquine, Drug: AzithromycinHydroxychloroquine + Azithromycin |
| Comparator 4 | Experimental | Drug: Hydroxychloroquine, Drug: OseltamivirHydroxychloroquine + Oseltamivir |
| Comparator 5 | Experimental | Drug: Oseltamivir, Drug: AzithromycinOseltamivir + Azithromycin |
| Comparator 6 | Experimental | Drug: Hydroxychloroquine, Drug: Oseltamivir, Drug: AzithromycinHydroxyquinine + Oseltamivir + Azithromycin |
| Observational Cohort | No intervention | –Non-consenting to randomization |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Confirmed SARS-CoV-2 (COVID-19) infection by a positive test result
- Either gender
- Symptomatic for example fever, dry Cough, difficulty to breathe
Key exclusion criteria (6 listed)
- Confirmed absence of SARS-CoV-2 (COVID-19) infection by a negative test result
- Have chronic conditions such as heart disease, liver and kidney failure
- Pregnant or currently lactating
- Immunocompromise and/or systemic disease(s)
- On other antiviral drugs
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxychloroquineHydroxychloroquine Sulfate (200 mg orally thrice a day for 5 days) | Drug | Comparator 3, Comparator 4, Comparator 6, Control Intervention |
| OseltamivirOseltamivir (75 mg orally twice a day for 5 days) | Drug | Comparator 2, Comparator 4, Comparator 5, Comparator 6 |
| AzithromycinAzithromycin (500 mg orally once a day on day 1, followed by 250 mg orally daily on days 2-5) | Drug | Comparator 1, Comparator 3, Comparator 5, Comparator 6 |
Primary outcome
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2022.
- Derived from this study: PubMed 38827854Azhar S, Akram J, Latif W, Ibanez NC, Mumtaz S, Rafi A, Aftab U, Iqtadar S, Shahzad M, Syed F, Zafar B, Fatima N, Afridi SS, Akram SJ, Chaudhary MA, Sadiq F, Goraya S, Hanif M, Ashraf V, Ashraf S, Akram H, Khaliq T. Effectiveness of early pharmaceutical interventions in symptomatic COVID-19 patients: A randomized clinical trial. Pak J Med Sci. 2024 May-Jun;40(5):800-810. doi: 10.12669/pjms.40.5.8757.
- Derived from this study: PubMed 35799756Azhar S, Akram J, Shahzad M, Latif W, Khan KS. Protocol of Pakistan randomized and observational trial to evaluate coronavirus treatment among newly diagnosed patients with COVID-19: Azithromycin, Oseltamivir, and Hydroxychloquine. Pak J Med Sci. 2022 May-Jun;38(5):1401-1408. doi: 10.12669/pjms.38.5.5512.
- Derived from this study: PubMed 32771032Akram 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.
- Individual participant dataSharing planned: Yes. On completion of study, investigators are open to participation in planned IPD projects with a prospective registration, subject to appropriate approvals
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Javed Akram, FRCP principal investigator
University of Health Sciences Lahore
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydroxychloroquine, Oseltamivir and Azithromycin in people with COVID 19, run by Shehnoor Azhar at 11 sites in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Laboratory Result (time frame: Day 07 on follow-up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04338698, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2022.