Covid19Phase 3COVID-19NCT04491994

Clearing the Fog: Is Hydroxychloroquine Effective in Reducing COVID-19 Progression

A Phase 3 study testing HCQ in people with Covid19 and Progression, run by UNICEF at 1 site in Pakistan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

Brief Summary: Purpose of this study is to evaluate efficacy of hydroxychloroquine (HCQ) in reducing progression of Corona Virus Disease 2019 (COVID - 19) and achieving viral clearance. Condition or disease :I COVID-19 ntervention/treatment :Drug: Hydroxychloroquine Sulfate Phase: Phase III Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Covid19, Progression
What is being tested?: HCQ
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 540 participants
Where: 1 sitePakistan
Study dates: 10 Apr 2020to 31 May 2020
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Mild Corona virus disease (COVID-19)
PCR confirmed infection
Hospital admitted patients

Who cannot join

Moderate, severe and critical COVID-19
day 0 CRP greater than 6mg/dl, ALC < 1000 or evidence of infiltrates on X-ray chest
comorbidity with life expectancy less than 6 months
Contraindications to HCQ therapy

Trial locations and contacts

1 site in 1 country.

Pakistan1 site

Pak Emirates Military Hospital
Rawalpindi, Punjab Province, 46000

Other trials in Pakistan

About this study

Official title: Clearing the Fog: Is HCQ Effective in Reducing COVID-19 progression-a Randomized Controlled Trial

Brief Summary: Purpose of this study is to evaluate efficacy of hydroxychloroquine (HCQ) in reducing progression of Corona Virus Disease 2019 (COVID - 19) and achieving viral clearance.

Condition or disease :I COVID-19 ntervention/treatment :Drug: Hydroxychloroquine Sulfate Phase: Phase III

Read the detailed description

This study explores efficacy of HCQ (400mg BD on D0 and 200mg BD D1-D5) in reducing progression of Mild Covid-19 patients and decreasing viral load.

Participants of study will be randomized 2:1 to receive either Active drug or standard of care (SOC) treatment respectively. We aim to demonstrate reduced COVID-19 progression and early viral clearance in individuals on HCQ therapy.

Conditions: Covid19, Progression
Being tested: HCQ
Keywords: COVID-19, viral clearance, , mild infection, disease progression, trial, HCQ
Medical subject headings: COVID-19, Disease Progression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

HCQDrug
Also called HCQ + Standard of Care (SOC)
Tab HCQ 400mg 12 hourly day 0 followed by tab HCQ 200mg 12 hrly for next 5 days

Study groups in NCT04491994
Study group	Role	What they receive
Standard of Care (SOC)	No intervention	Patients selected in supportive arm will be given daily standard doses of oral Vit C (2g), Vit D (alfacalcidiol 1µg), Zinc (50mg) and paracetamol (as required).
HCQ arm	Experimental	Patients selected in experimental arm will be given Tab HCQ (400mg BD on D0 followed by 200mg BD D1-D5) in addition to supportive treatment Receives: Drug: HCQ

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Progression
After start of treatment, development of fever > 101 F for > 72 hours, shortness of breath by minimal exertion (10-Step walk test), derangement of basic lab parameters (ALC < 1000 or raised CRP) or appearance of infiltrates on CXR during course of treatment was labeled as progression irrespective of PCR status
Measured: 5 days

Secondary outcomes (1)

Viral Clearance
PCR negativity on day 7 and 14 after admission
Measured: 14 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Apr 202031 May 2020

First posted30 Jul 2020
Study start10 Apr 2020
Primary completion31 May 2020
Study completion31 May 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (8)Papers the sponsor has linked to this study.
Other trials for Covid19Studies 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: Randomization rules were designed by Dr. Wasim Alamgir together with principal investigators and implemented by an independent statistician who was not involved in data analysis. Stratified random sampling was applied to stratify all eligible patients according to age, gender and comorbidities. Computerized random number generator was used and allocation was done in 2:1 sequence. Cards with each group assignment number randomly generated by computer were placed in sequentially numbered envelopes that were opened as the patients were enrolled
Masking: None (open label)
Enrolment: 540 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04491994
Sponsor's protocol ID: Sultan Mehmood Kamran 2
Acronym: COVID-19
Status last verified: Aug 2020
First submitted: 28 Jul 2020
Last updated: 21 Aug 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: data can be shared on demand in SPSS sheet

Publications

Biot C, Daher W, Chavain N, Fandeur T, Khalife J, Dive D, De Clercq E. Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities. J Med Chem. 2006 May 4;49(9):2845-9. doi: 10.1021/jm0601856.
PubMed 16640347
Murray JJ, Lee MS. Re: Marmor et al.: American Academy of Ophthalmology Statement: Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 Revision). (Ophthalmology 2016;123:1386-1394). Ophthalmology. 2017 Mar;124(3):e28-e29. doi: 10.1016/j.ophtha.2016.06.062. No abstract available.
PubMed 28219513
Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honore S, Colson P, Chabriere E, La Scola B, Rolain JM, Brouqui P, Raoult D. RETRACTED: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Jul;56(1):105949. doi: 10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20.
PubMed 32205204
Zhou D, Dai SM, Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother. 2020 Jul 1;75(7):1667-1670. doi: 10.1093/jac/dkaa114.
PubMed 32196083
Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Jul 28;71(15):732-739. doi: 10.1093/cid/ciaa237.
PubMed 32150618
Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16;14(1):72-73. doi: 10.5582/bst.2020.01047. Epub 2020 Feb 19.
PubMed 32074550
Chen J, Liu D, Liu L, Liu P, Xu Q, Xia L, Ling Y, Huang D, Song S, Zhang D, Qian Z, Li T, Shen Y, Lu H. [A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020 May 25;49(2):215-219. doi: 10.3785/j.issn.1008-9292.2020.03.03. Chinese.
PubMed 32391667
Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, Cheng VC, Edwards KM, Gandhi R, Muller WJ, O'Horo JC, Shoham S, Murad MH, Mustafa RA, Sultan S, Falck-Ytter Y. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Clin Infect Dis. 2020 Apr 27:ciaa478. doi: 10.1093/cid/ciaa478. Online ahead of print.
PubMed 32338708

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 21 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Clearing the Fog: Is HCQ Effective in Reducing COVID-19 progression-a Randomized Controlled Trial
ClinicalTrials.gov ID: NCT04491994
Acronym / sponsor ID: COVID-19 / Sultan Mehmood Kamran 2
Conditions: Covid19, Progression
Keywords: COVID-19, viral clearance, , mild infection, disease progression, trial, HCQ
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 540 participants (actual)
Lead sponsor: UNICEFUniversity, hospital or other
Collaborators: Pak Emirates Military Hospital
Study start: 10 Apr 2020 (actual)
Primary completion: 31 May 2020 (actual)
Study completion: 31 May 2020 (actual)
First posted: 30 Jul 2020 (actual)
Results: Posted 21 Aug 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Brief Summary: Purpose of this study is to evaluate efficacy of hydroxychloroquine (HCQ) in reducing progression of Corona Virus Disease 2019 (COVID - 19) and achieving viral clearance.

Condition or disease :I COVID-19 ntervention/treatment :Drug: Hydroxychloroquine Sulfate Phase: Phase III

Detailed description

This study explores efficacy of HCQ (400mg BD on D0 and 200mg BD D1-D5) in reducing progression of Mild Covid-19 patients and decreasing viral load.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: Randomization rules were designed by Dr. Wasim Alamgir together with principal investigators and implemented by an independent statistician who was not involved in data analysis. Stratified random sampling was applied to stratify all eligible patients according to age, gender and comorbidities. Computerized random number generator was used and allocation was done in 2:1 sequence. Cards with each group assignment number randomly generated by computer were placed in sequentially numbered envelopes that were opened as the patients were enrolled

Arm	Type	Receives
Standard of Care (SOC)	No intervention	–Patients selected in supportive arm will be given daily standard doses of oral Vit C (2g), Vit D (alfacalcidiol 1µg), Zinc (50mg) and paracetamol (as required).
HCQ arm	Experimental	Drug: HCQPatients selected in experimental arm will be given Tab HCQ (400mg BD on D0 followed by 200mg BD D1-D5) in addition to supportive treatment

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Mild Corona virus disease (COVID-19)
PCR confirmed infection
Hospital admitted patients

Key exclusion criteria (4 listed)

Moderate, severe and critical COVID-19
day 0 CRP greater than 6mg/dl, ALC < 1000 or evidence of infiltrates on X-ray chest
comorbidity with life expectancy less than 6 months
Contraindications to HCQ therapy

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
HCQAlso: HCQ + Standard of Care (SOC)Tab HCQ 400mg 12 hourly day 0 followed by tab HCQ 200mg 12 hrly for next 5 days	Drug	HCQ arm

Primary outcome

Number of Participants With Progression
Time frame: 5 days
After start of treatment, development of fever > 101 F for > 72 hours, shortness of breath by minimal exertion (10-Step walk test), derangement of basic lab parameters (ALC < 1000 or raised CRP) or appearance of infiltrates on CXR during course of treatment was labeled as progression irrespective of PCR status

1 secondary outcome

Viral Clearance
Time frame: 14 days

Results and safety

Results posted to the registry on 21 Aug 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Control Group	180	151
Intervention Group	360	349

Primary outcome: Number of Participants With Progression

Time frame: 5 days. Count of participants. Unit: Participants

Measure	Standard of Care (SOC) n = 151	Intervention Group n = 349
Value	5	11

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 14 days after first dose of HCQ or SOC. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Control Group	0 of 151 (0%)	0 of 151 (0%)	0 of 151
Intervention Group	0 of 349 (0%)	0 of 349 (0%)	0 of 349

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 16640347Biot C, Daher W, Chavain N, Fandeur T, Khalife J, Dive D, De Clercq E. Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities. J Med Chem. 2006 May 4;49(9):2845-9. doi: 10.1021/jm0601856.
Background: PubMed 28219513Murray JJ, Lee MS. Re: Marmor et al.: American Academy of Ophthalmology Statement: Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 Revision). (Ophthalmology 2016;123:1386-1394). Ophthalmology. 2017 Mar;124(3):e28-e29. doi: 10.1016/j.ophtha.2016.06.062. No abstract available.
Background: PubMed 32205204Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honore S, Colson P, Chabriere E, La Scola B, Rolain JM, Brouqui P, Raoult D. RETRACTED: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Jul;56(1):105949. doi: 10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20.
Background: PubMed 32196083Zhou D, Dai SM, Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother. 2020 Jul 1;75(7):1667-1670. doi: 10.1093/jac/dkaa114.
Background: PubMed 32150618Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Jul 28;71(15):732-739. doi: 10.1093/cid/ciaa237.
Background: PubMed 32074550Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16;14(1):72-73. doi: 10.5582/bst.2020.01047. Epub 2020 Feb 19.
Background: PubMed 32391667Chen J, Liu D, Liu L, Liu P, Xu Q, Xia L, Ling Y, Huang D, Song S, Zhang D, Qian Z, Li T, Shen Y, Lu H. [A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020 May 25;49(2):215-219. doi: 10.3785/j.issn.1008-9292.2020.03.03. Chinese.
Background: PubMed 32338708Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, Cheng VC, Edwards KM, Gandhi R, Muller WJ, O'Horo JC, Shoham S, Murad MH, Mustafa RA, Sultan S, Falck-Ytter Y. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Clin Infect Dis. 2020 Apr 27:ciaa478. doi: 10.1093/cid/ciaa478. Online ahead of print.
Individual participant dataSharing planned: Yes. data can be shared on demand in SPSS sheet

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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.

Imran m Fazal, FCPS study director

Pak Emirates Military Hospital (PEMH) Rawalpindi

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing HCQ in people with Covid19 and Progression, run by UNICEF at 1 site 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 4 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 21 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Yes. Results are posted in the registry (first posted 21 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Progression (time frame: 5 days). 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 NCT04491994, which also lists 8 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 21 Aug 2020.