FAvipiravir and HydroxyChloroquine Combination Therapy (FACCT)

• ClinicalTrials.gov Identifier: NCT04392973
• Recruitment Status: Completed
• First Posted: May 19, 2020
• Last Update Posted: August 20, 2021
• Sponsor: King Abdullah International Medical Research Center
• Information provided by (Responsible Party): King Abdullah International Medical Research Center

Study Description

Brief Summary:

This study is a randomized, open-label, parallel groups multi-centered trial were participants are assigned to either an intervention arm ( a combination of Favipiravir and Hydroxychloroquin) or standard of care.

Condition or disease	Intervention/treatment	Phase
COVID19	Combination Product: Favipiravir and Hydroxychloroquine	Not Applicable

Detailed Description:

In this trial, the investigators want to evaluate the efficacy of the combination of Favipiravir and Hydroxychloroquine as potential therapy for moderate and severe cases with COVID -19. Favipiravir which is a new type of RNA-dependent RNA polymerase (RdRp) inhibitor has activity against influenza virus, and Hydroxychloroquine, an analogue of chloroquine, has a clinical safety profile better than that of chloroquine and allows higher daily dose, Chloroquine is a widely used antimalarial that was found to be a potential broad-spectrum antiviral.

There is an urgent need to explore therapeutic options for SARS-CoV-2 in order to face the pandemic. The selected combination was based on limited evidence clinically and in vitro on the efficacy of the Favipiravir and Hydroxychloroquine in SARS-CoV-2. The two medications were listed in many guidelines as treatment options and ongoing trials assessing their efficacy and safety. Thus, the investigators want to prove the effectiveness of the combination as therapy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 268 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, open-label, parallel groups were participants are assigned to either an intervention arm or standard of care.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Trial of Favipiravir and Hydroxychloroquine Combination in Adults Hospitalized With Moderate and Severe Covid-19
• Actual Study Start Date: May 21, 2020
• Actual Primary Completion Date: January 26, 2021
• Actual Study Completion Date: April 26, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention; Combination therapy Favipiravir (10 days) + Hydroxychloroquine(5 days)	Combination Product: Favipiravir and Hydroxychloroquine; Route of Administration: Oral (or through Nasogastric tube) Dose: Favipiravir: Administer 1800 mg (9 tablets) by mouth twice daily for one day, followed by 800mg (4 tablets) twice daily (total days of therapy is 10 days or till hospital discharge) Hydroxychloroquine (400mg) twice daily on day 1; for days 2-5 (200mg) twice daily.; Other Name: Avigan
No Intervention: Control; Standard of Care Treatment for COVID-19 Infection

Outcome Measures

Primary Outcome Measures :

1. Clinical Improvement [ Time Frame: 28 days ]
   The primary endpoint is the time to clinical improvement, defined as the time from the randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first.

Secondary Outcome Measures :

1. Viral shedding [ Time Frame: 28 days ]
   PCR test negative conversion days from positive to negative.

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. Should be at least 18 years of age
2. Male or nonpregnant female,
3. Diagnosed with COVID-19 by PCR confirmed SARS-coV-2 viral infection.
4. Able to sign the consent form and agree to clinical samples collection (or their legal surrogates if subjects are or become unable to make informed decisions).
5. Moderate or Severe COVID-19, defined as oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or significant clinical symptoms with Chest X ray changes that require hospital admission.
6. patients had to be enrolled within 10 days of disease onset

Exclusion Criteria:

1. Patients who are pregnant or breastfeeding.
2. Will be transferred to a non-study site hospital or expected to be discharged within 72 hours.
3. Known sensitivity/allergy to hydroxychloroquine or Favipiravir
4. Current use of hydroxychloroquine for another indication
5. Prior diagnosis of retinopathy
6. Prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency
7. Major comorbidities increasing the risk of study drug including: i. Hematologic malignancy, ii. Advanced (stage 4-5) chronic kidney disease or dialysis therapy, iii. Known history of ventricular arrhythmias, iv. Current use of drugs that prolong the QT interval, Severe liver damage (Child-Pugh score ≥ C, AST> 5 times the upper limit), HIV.
8. The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues).
9. Clinical prognostic non-survival, palliative care, or in deep coma and no have response to supportive treatment within three hours of admission.
10. Patient with irregular rhythm
11. Patient with a history of heart attack (myocardial infarction)
12. Patient with a family history of sudden death from heart attack before the age of 50
13. Take other drugs that can cause prolonged QT interval
14. Patient who is receiving immunosuppressive therapy (cyclosporin) which cannot be switched to another agent or adjusted while using the investigational drug
15. Gout/history of Gout or hyperuricemia (above the ULN), hereditary xanthinuria or xanthine calculi of the urinary tract.

Contacts and Locations

Locations

Saudi Arabia

King Abdulaziz Hospital - Al Ahsa

Hasa, Eastern Region, Saudi Arabia

AlMadina General Hospital

Al Madīnah, Saudi Arabia

Al-Qatif Central Hospital

Al-Qatif, Saudi Arabia

Imam Abdulrahman Al Faisal Hospital - Dammam

Dammam, Saudi Arabia

King Abdulaziz Medical City

Jeddah, Saudi Arabia

King Abdulaziz Hospital - Makkah

Mecca, Saudi Arabia

King Abdulaziz Medical City, National Guard Health Affairs

Riyadh, Saudi Arabia, 11426

Imam Abdulrahman Alfaisal Hospital

Riyadh, Saudi Arabia

Sponsors and Collaborators

King Abdullah International Medical Research Center

Investigators

• Study Director: Ahmad Alaskar; KAIMRC

More Information

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

Bosaeed M, Mahmoud E, Alharbi A, Altayib H, Albayat H, Alharbi F, Ghalilah K, Al Arfaj A, AlJishi J, Alarfaj A, Alqahtani H, Almutairi BM, Almaghaslah M, Alyahya NM, Bawazir A, AlEisa S, Alsaedy A, Bouchama A, Alharbi M, AlShamrani M, Al Johani S, Aljeraisy M, Alzahrani M, Althaqafi AO, Almarhabi H, Alotaibi A, Alqahtani N, Arabi YM, Aldibasi OS, Alaskar A. Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID-19 (FACCT Trial): An Open-Label, Multicenter, Randomized, Controlled Trial. Infect Dis Ther. 2021 Dec;10(4):2291-2307. doi: 10.1007/s40121-021-00496-6. Epub 2021 Jul 28.

Bosaeed M, Mahmoud E, Hussein M, Alharbi A, Alsaedy A, Alothman A, Aljeraisy M, Alqahtani H, Nashabat M, Almutairi B, Almaghaslah M, Aldibasi O, AlJohani S, Bouchama A, Arabi Y, Alaskar A. A Trial of Favipiravir and Hydroxychloroquine combination in Adults Hospitalized with moderate and severe Covid-19: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Oct 31;21(1):904. doi: 10.1186/s13063-020-04825-x.

• Responsible Party: King Abdullah International Medical Research Center
• ClinicalTrials.gov Identifier: NCT04392973
• Other Study ID Numbers: RC20/174
• First Posted: May 19, 2020
• Last Update Posted: August 20, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by King Abdullah International Medical Research Center:

SARS-CoV-2

Additional relevant MeSH terms:

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