Chemoprevention Clinical Trial of COVID-19: Hydroxychloroquine Post Exposure Prophylaxis

NCT04597775 | Unknown Phase 2 DMC

• 1 other identifier: APCC-19
• Study Type: interventional
• Target: 93
• Locations: 0 countries
• Sites: N/A

Brief Summary

Protocol summary Title A Prospective, randomized, adaptive phase II/III clinical trial, controlled, open-label, chemoprevention, 3-arms, parallel, multi-centred, to A Prospective, randomized, clinical trial, controlled, open-label, 3-arms, parallel, multi-centred, chemoprevention of COVID-19: Hydroxychloroquine Post Exposure Prophylaxis For COVID-19 Study Periods \& Duration of Treatment Study Duration: 6 months Approval (IRB and regulatory bodies) 1 month Recruitment and follow-up: 3 months Analysis, report writing and submission of publications 1 month This study is a parallel study of one period with an expected duration of treatment (for each subject) of 28 days, Objectives

• To evaluate if hydroxychloroquine with the proposed dose can provide potent chemoprophylaxis against the development of COVID-19 positive patients in subjects who had primary exposure to COVID-19 positive patients.
• To measure the incidence of potential adverse drug reaction rates for giving hydroxychloroquine for prevention of COVID-19 amongst close contacts
• To provide early analysis of results and redefine sample size accordingly.
• identifying subjects most likely to benefit during the phase II and focusing recruitment efforts on them during phase III
• stopping one arm or the whole trial at an early stage for success or lack of efficacy based on phase II study results Design Prospective, Randomized, open-label, three-arm, parallel, adaptive phase II/III controlled study in which subjects will be randomly assigned in a 1:1:1 ratio as per the following: Arm-1: hydroxychloroquine 800mg (400mg twice daily) given orally on day 1, (loading dose) hydroxychloroquine. Then 400mg (200mg 2 tablets) on day 2,3, 4 and 5. Arm-2: hydroxychloroquine 400mg (200mg twice daily) Given orally first day (loading dose), then 200mg once daily on day 2,3, 4 and 5. Arm-3: No Intervention- SARS-CoV-2 surveillance Standard control measures in the country of interest such as self isolation, good personal hygiene and good nutrition.

Conditions

SARS-CoV Infection

Keywords

COVID-19; SARS-CoV-2; Chemoprevention; Primary contact; Hydroxychloroquine; prophylaxis

Outcome Measures

Primary Outcomes (2)

• Incidence rate of COVID-19 on day 14 according to positive results of RT-PCR rate at day 14

  Study will seek to find direct correlation between the administration of Hydroxychloroquine and incidence of COVID-19: A reduced positive RT-PCR samples in subjects who were exposed to COVID-19patients. Positive RT-PCR samples in close contacts on day 14 of randomization.

  14 days

• Safety and adverse events (AEs) incidence rate at day 14

  Safety and adverse events (AEs) incidence rate at day 14

  14 days

Secondary Outcomes (3)

• IgM antibodies positive rate for COVID-19 at day 28

  28 days

• Incidence rate of COVID-19 on day 28 according to positive results of RT-PCR rate at day 28

  28 days

• Safety and adverse events (AEs) incidence rate on day 28

  28 days

Study Arms (3)

Arm 1 hydroxychloroquine 800mg day 1 and hydroxychloroquine 400mg day 2-5

EXPERIMENTAL

hydroxychloroquine 800mg (400mg twice daily) given orally on day 1, (loading dose) hydroxychloroquine. Then 400mg (200mg 2 tablets) on day 2,3, 4 and 5.

Drug: hydroxychloroquine

Arm 2 hydroxychloroquine 400mg day 1 and hydroxychloroquine 200mg day 2-5

ACTIVE COMPARATOR

hydroxychloroquine 400mg (200mg twice daily) Given orally first day (loading dose), then 200mg once daily on day 2,3, 4 and 5.

Drug: hydroxychloroquine

No Intervention

NO INTERVENTION

No Intervention- SARS-CoV-2 surveillance Standard control measures in the country of interest such as self isolation, good personal hygiene and good nutrition.

Interventions

hydroxychloroquine DRUG

hydroxychloroquine

Also known as: plaquenil

Arm 1 hydroxychloroquine 800mg day 1 and hydroxychloroquine 400mg day 2-5; Arm 2 hydroxychloroquine 400mg day 1 and hydroxychloroquine 200mg day 2-5

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary contacts, described below, aged 18 to 65 years and having provide Written informed consent by the patient, by the patient's legal /authorized representative as applicable.
• According to below criteria, as soon as a new subject in identified, he/she will be consented for reaching his contacts according to below criteria. The research team within 48 hours of index case identification will call his/her contacts who fulfill below criteria for participation in the trial. All potential participants will be tested using RT-PCR and IgM and IgG antibodies to rule out current or previous disease status.
• Contact is a person free from COVID-19 who experienced any one of the following exposures during the 2 days before and the 14 days after the onset of symptoms of a probable or confirmed case:
• A person living in the same household as a COVID-19 case
• A person having had direct physical contact with a COVID-19 case (e.g. shaking hands)
• A person having unprotected direct contact with infectious secretions of a COVID-19 case (e.g. being coughed on, touching used paper tissues with a bare hand)
• A person having had face-to-face contact with a COVID-19 case within 2 meters \[2\] and \> 15 minutes
• A person who was in a closed environment (e.g. classroom, meeting room, hospital waiting room, etc.) with a COVID-19 case for 15 minutes or more and at a distance of less than 2 meters
• A healthcare worker (HCW) or other person providing direct care for a COVID-19 case, or laboratory workers handling specimens from a COVID-19 case without recommended personal protective equipment or with a possible breach of personal protective equipment use policies
• A contact in an aircraft sitting within two seats (in any direction) of the COVID-19 case, travel companions or persons providing care, and crew members serving in the section of the aircraft where the index case was seated (if severity of symptoms or movement of the case indicate more extensive exposure, passengers seated in the entire section or all passengers on the aircraft may be considered close contacts)

You may not qualify if:

• Women who are pregnant (at the time of screening) or breastfeeding
• known hypersensitivity or allergy to hydroxychloroquine or other aminoquinoline compounds
• History of severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis
• History of pre-existing retinopathy or maculopathy,
• concomitant use of tamoxifen
• History of congenital or acquired long QT-interval, current use of drugs that prolong the QT interval,
• family history of long QT arrythmia, cardiac disease such as heart failure, myocardial infarction
• concurrent use of anti-arrhythmic drugs, or family history of sudden cardiac death, or sudden cardiac death, bradycardia \< 50 beats/min, uncorrected hypokalemia or hypomagnesemia
• severe renal disease or patients receiving dialysis
• Patients less than 35 kg bodyweight
• Currently taking Hydroxychloroquine
• Suspected or confirmed current COVID-19, defined as: (1) temperature \> 38 Celsius; (2) cough; (3) shortness of breath; (4) sore throat; or, if available (not required), (5) positive confirmatory testing for COVID-19
• Inability to take medications orally
• Inability to provide written consent
• With significantly abnormal liver function

Sponsors & Collaborators

• Regional Center for Disease Control and Prevention, Jordan: lead
• Farhat Hached Hospital, Tunisia: collaborator
• Fattouma Bourguiba, Tunisia: collaborator

MeSH Terms

Conditions

Severe Acute Respiratory Syndrome; COVID-19

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Munir Abu-Helalah, PHD

  Regional Center for Disease Control

  PRINCIPAL INVESTIGATOR

• Wissem Hachfi, MD

  Farhat Hached Hospital, Tunisia

  STUDY CHAIR

Central Study Contacts

Munir A Abu-Helalah, PhD

CONTACT

00962795912413; mabuhelalah@yahoo.co.uk

Amer A Amous, MD

CONTACT

00962797950001; amer.amous@rcdcp.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Executive Officer

Model Details: Prospective, Randomized, open-label, three-arm, parallel, adaptive phase II/III controlled study in which subjects will be randomly assigned in a 1:1:1 ratio as per the following: Arm-1: hydroxychloroquine 800mg (400mg twice daily) given orally on day 1, (loading dose) hydroxychloroquine. Then 400mg (200mg 2 tablets) on day 2,3, 4 and 5. Arm-2: hydroxychloroquine 400mg (200mg twice daily) Given orally first day (loading dose), then 200mg once daily on day 2,3, 4 and 5. Arm-3: No Intervention- SARS-CoV-2 surveillance Standard control measures in the country of interest such as self isolation, good personal hygiene and good nutrition.

Study Record Dates

• First Submitted: October 18, 2020
• First Posted: October 22, 2020
• Study Start: October 27, 2020
• Primary Completion: January 15, 2021
• Study Completion: January 31, 2021
• Last Updated: October 22, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share