FAvipiravir and HydroxyChloroquine Combination Therapy (FACCT)

A Trial of Favipiravir and Hydroxychloroquine Combination in Adults Hospitalized With Moderate and Severe Covid-19

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.

Study Overview

• Status: Completed
• Conditions: COVID19
• Intervention / Treatment: Combination product: Favipiravir and Hydroxychloroquine

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 Type: Interventional
• Enrollment (Actual): 268
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Saudi Arabia
  • Al Madīnah, Saudi Arabia
    • AlMadina General Hospital
  • Al-Qatif, Saudi Arabia
    • Al-Qatif Central Hospital
  • Dammam, Saudi Arabia
    • Imam Abdulrahman Al Faisal Hospital - Dammam
  • Jeddah, Saudi Arabia
    • King Abdulaziz Medical City
  • Mecca, Saudi Arabia
    • King Abdulaziz Hospital - Makkah
  • Riyadh, Saudi Arabia, 11426
    • King Abdulaziz Medical City, National Guard Health Affairs
  • Riyadh, Saudi Arabia
    • Imam Abdulrahman Alfaisal Hospital
  • Eastern Region
    • Hasa, Eastern Region, Saudi Arabia
      • King Abdulaziz Hospital - Al Ahsa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: Avigan
No Intervention: Control; Standard of Care Treatment for COVID-19 Infection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Improvement	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.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral shedding	PCR test negative conversion days from positive to negative.	28 days

Collaborators and Investigators

• Sponsor: King Abdullah International Medical Research Center
• Investigators: Study Director: Ahmad Alaskar, KAIMRC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2020
• Primary Completion (Actual): January 26, 2021
• Study Completion (Actual): April 26, 2021

Study Registration Dates

• First Submitted: May 10, 2020
• First Submitted That Met QC Criteria: May 13, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Actual): August 20, 2021
• Last Update Submitted That Met QC Criteria: August 19, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Favipiravir; Hydroxychloroquine
• Other Study ID Numbers: RC20/174

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No