Clinical trial NCT04392973: FAvipiravir and HydroxyChloroquine Combination Therapy
Official title: A Trial of Favipiravir and Hydroxychloroquine Combination in Adults Hospitalized With Moderate and Severe Covid-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COVID19
Keywords: SARS-CoV-2
Lead sponsor: King Abdullah International Medical Research Center
Sponsor class: OTHER
First posted: 2020-05-19
Enrollment: 268
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, open-label, parallel groups were participants are assigned to either an intervention arm or standard of care.
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Clinical Improvement
timeFrame: 28 days
Secondary outcomes:
measure: Viral shedding
timeFrame: 28 days
Other outcomes:
Locations:
city: Hasa
country: Saudi Arabia
facility: King Abdulaziz Hospital - Al Ahsa
state: Eastern Region
city: Al Madīnah
country: Saudi Arabia
facility: AlMadina General Hospital
city: Al-Qatif
country: Saudi Arabia
facility: Al-Qatif Central Hospital
city: Dammam
country: Saudi Arabia
facility: Imam Abdulrahman Al Faisal Hospital - Dammam
city: Jeddah
country: Saudi Arabia
facility: King Abdulaziz Medical City
city: Mecca
country: Saudi Arabia
facility: King Abdulaziz Hospital - Makkah
city: Riyadh
country: Saudi Arabia
facility: King Abdulaziz Medical City, National Guard Health Affairs
city: Riyadh
country: Saudi Arabia
facility: Imam Abdulrahman Alfaisal Hospital
Study officials:
affiliation: KAIMRC
name: Ahmad Alaskar
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.