Efficacy of Various Doses of Hydroxychloroquine in Pre-Exposure Prophylaxis for COVID 19

NCT ID: NCT04359537

Last Updated: 2020-05-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-01
• Study Completion Date: 2020-09-25

Brief Summary

Hydroxychloroquine has been approved by FDA as one of the treatment options for COVID 19.Healthcare personnel are amongst those at highest risk to contract the disease. Several health authorities are now recommending the use of hydroxychloroquine as pre-exposure prophylaxis is in health care personnel. Several studies are on going in this context. However there is a controversy regarding the dosage regimen. This drug has a half life of 22.4 days. In this study we will be comparing three different doses of Hydroxychloroquine and additionally have a control group in order to determine the efficacy of hydroxychloroquine as pre- exposure prophylaxis in healthcare personnel in various doses.

Detailed Description

Study design:

Phase 2 proof of concept study Study Type: Interventional (Clinical Trial) Estimated Enrollment : at least 200 participants Since the investigators have no current data on pre-exposure prophylaxis to calculate sample size statistically, so a minimum of 50 participants in each arm will be recruited including 20% attrition rate. The investigators will be recruiting a minimum of 200 participants in the study , that is at least 50 in each of the four arms.

Allocation: Randomized Intervention Model: Parallel Assignment Study model: Parallel group interventional study Location: SZABMU/PIMS Study duration: a minimum of 12 weeks from recruitment

Materials and Methods:

Participants will be recruited after approval from Ethical Review Board .A written informed consent will be taken from all participants. Participants fulfilling the eligibility criteria will be randomized to 4 arms.

Arm Intervention /treatment

Experimental group 1: Hydroxychloroquine 400 mg twice a day 1,followed by 400 mg weekly for a total of 12 weeks Drug: Hydroxychloroquin HCQ 200 mg, oral

Experimental group 2:Hydroxychloroquine 400 mg on day 1 followed by 400mg once every 3 weeks for a total of 12 weeks Drug: Hydroxychloroquin HCQ 200 mg, oral

Experimental group 3:Hydroxychloroquine 200 mg on day 1 followed by 200 mg once every 3 weeks for a total of 12 weeks Drug: Hydroxychloroquin HCQ 200 mg, oral

Control Group : Placebo 200mg will be given on day 1 followed by Placebo 200mg every three weeks for a total of 12 weeks.

Base line characteristics of all participants will be recorded including age ,gender,role of healthcare personnel, comorbidities, and drugs the participant is using.

Samples will be collected for complete picture blood, liver and renal function tests and electrocardiogram. These tests will also be conducted every month till the end of the trial and the participants will be monitored for any adverse effects.

During the study duration all participants will self- report any symptoms related to COVID 19 and any adverse reactions from the drug. Participants having COVID 19 symptoms at any time will be tested by the gold standard test PCR for SARS-COV-2 using nasopharyngeal and oropharyngeal swabs.

All participants at the end of the study will have PCR for SARS-COV-2 and if available IgM and IgG serology to find out if they had any infection, did not get infected at all or only had asymptomatic or mild infection.

Conditions

COVID 19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Arm 1

Hydroxychloroquine Sulphate will be administered at a dose of 400mg twice a day on day 1 followed by 400 mg once a week for a total of 12 weeks

Group Type: EXPERIMENTAL

Hydroxychloroquine Sulfate 200 MG

Intervention Type: DRUG

Hydroxychloroquine Sulphate 200 mg tablets will be prescribed and instituted orally at the doses and regimens described

Arm 2

Hydroxychloroquine Sulphate will be admoinistered at a dose of 400 mg on day 1 followed by 400mg once every 3 weeks for at total of 12 weeks

Group Type: EXPERIMENTAL

Hydroxychloroquine Sulfate 200 MG

Intervention Type: DRUG

Hydroxychloroquine Sulphate 200 mg tablets will be prescribed and instituted orally at the doses and regimens described

Arm 3

Hydroxychloroquine Sulphate will be administered at a dose of 200 mg on day 1 followed by 200 mg once every 3 weeks for a total of 12 weeks

Group Type: EXPERIMENTAL

Hydroxychloroquine Sulfate 200 MG

Intervention Type: DRUG

Hydroxychloroquine Sulphate 200 mg tablets will be prescribed and instituted orally at the doses and regimens described

Arm 4

Control group will recieve Placebo 200mg on day 1 followed by Placebo 200mg every three weeks for 12 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Control group will receive a Placebo tablet. Placebo 200mg will be given on Day 1 followed by Placebo 200mg every three weeks.

Interventions

Hydroxychloroquine Sulfate 200 MG

Hydroxychloroquine Sulphate 200 mg tablets will be prescribed and instituted orally at the doses and regimens described

Intervention Type: DRUG

Placebo

Control group will receive a Placebo tablet. Placebo 200mg will be given on Day 1 followed by Placebo 200mg every three weeks.

Intervention Type: OTHER

Other Intervention Names

Tab HCQ

Eligibility Criteria

Inclusion Criteria

• A healthcare worker at high risk for COVID19 exposure (defined below):

• Persons primarily working in emergency departments (physicians, nurses, ancillary staff, triage personnel) ;
• Persons primarily working in intensive care units (physicians, nurses, ancillary staff, respiratory therapists) ;
• Persons performing aerosol generating procedures (i.e. anesthesiologists, nurse anesthetists, gastroenterologists performing endoscopy, Pulmonologists performing bronchoscopy);
• First responders (i.e. EMTs, paramedics) ;
• Persons working in the departments of General Medicine, Pulmonology, Infectious disease and Isolation wards.

Exclusion Criteria

• Active COVID-19 disease;
• Confirmed prior COVID-19 disease;
• Current fever, cough, shortness of breath;
• Contraindication or hypersensitivity to chloroquine or hydroxychloroquine ad hypersensitivity to 4-aminoquinoline compounds;
• Pregnancy;
• Lactation;
• Prior retinal eye disease;
• Known Chronic Kidney disease, Stage 4 or 5 or dialysis;
• Known glucose-6 phosphate dehydrogenase (G-6-PD) deficiency ;
• Weight <40 kg;
• Current use of chloroquine,hydroxychloroquine or cardiac medicines like flecainide, amiodarone, digoxin, procainamide, or propafenone;
• Current use of medications with known significant drug-drug interactions: artemether, lumefantrine, mefloquine, tamoxifen or methotrexate;
• Current use of medications causing QT interval prolongation like: macrolides,antipsychotics,quinolones,antihistamines,SSRIs,tricyclic antidepressants, antifungals;
• Recent Myocardial Infarction;
• History of Epilepsy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shaheed Zulfiqar Ali Bhutto Medical University

OTHER

Sponsor Role: lead

Responsible Party

Fibhaa Syed

Assistan Professor Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fibhaa Syed, FRCP

Role: PRINCIPAL_INVESTIGATOR

Shaheed Zylfiqar Ali Bhutto Medical University

Mohammed Ali Arif, FRCP

Role: PRINCIPAL_INVESTIGATOR

Shaheed Zulfiqar Ali Bhutto Medical University

Rauf Niazi, FRCP

Role: STUDY_DIRECTOR

Shaheed Zulfiqar Ali Bhutto Medical University /PIMS

Locations

Shaheed Zulfiaqar Ali Bhutto Medical University

Islamabad, Federal Capital, Pakistan

Site Status: RECRUITING

Countries

Pakistan

Central Contacts

Fibhaa Syed, FRCP

Role: CONTACT

drfibhasyed@szabmu.edu.pk

+923335300002 ext. +923335300002

Mohammed Ali Arif, FRCP

Role: CONTACT

mohammad_ali_arif@hotmail.com

+923335123701 ext. +923335123701

Facility Contacts

Fibhaa Syed, FRCP

Role: primary

fibhaasyed@gmail.com

+923335300002 ext. +923335300002

Mohammed Ali Ali Arif, FRCP

Role: backup

mohammad_ali_arif@hotmail.com

+923335123701

References

Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Sevestre J, Mailhe M, Doudier B, Aubry C, Amrane S, Seng P, Hocquart M, Eldin C, Finance J, Vieira VE, Tissot-Dupont HT, Honore S, Stein A, Million M, Colson P, La Scola B, Veit V, Jacquier A, Deharo JC, Drancourt M, Fournier PE, Rolain JM, Brouqui P, Raoult D. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study. Travel Med Infect Dis. 2020 Mar-Apr;34:101663. doi: 10.1016/j.tmaid.2020.101663. Epub 2020 Apr 11.

Reference Type: BACKGROUND

PMID: 32289548 (View on PubMed)

Mack HG. Hydroxychloroquine use during the COVID-19 pandemic 2020. Aust J Gen Pract. 2020 Apr 14;49. doi: 10.31128/AJGP-COVID-08.

Reference Type: BACKGROUND

PMID: 32294807 (View on PubMed)

Xiang YT, Jin Y, Wang Y, Zhang Q, Zhang L, Cheung T. Tribute to health workers in China: A group of respectable population during the outbreak of the COVID-19. Int J Biol Sci. 2020 Mar 15;16(10):1739-1740. doi: 10.7150/ijbs.45135. eCollection 2020.

Reference Type: BACKGROUND

PMID: 32226292 (View on PubMed)

Khan S, Siddique R, Ali A, Bai Q, Li Z, Li H, Shereen MA, Xue M, Nabi G. The spread of novel coronavirus has created an alarming situation worldwide. J Infect Public Health. 2020 Apr;13(4):469-471. doi: 10.1016/j.jiph.2020.03.005. Epub 2020 Apr 2. No abstract available.

Reference Type: BACKGROUND

PMID: 32247752 (View on PubMed)

Other Identifiers

F.1-1/2015/ERB/SZABMU/549

Identifier Type: -

Identifier Source: org_study_id