Clinical trial NCT03787459: Severe Influenza Trial of ARbidol
Official title: Oseltamivir and Arbidol Combination Antiviral Therapy Versus Oseltamivir Monotherapy for the Treatment of Severe inﬂuenza: a Multicentre, Double-blind, Randomised Phase 3 Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Influenza
Keywords: severe influenza, arbidol, oseltamivir, ordinal scale
Lead sponsor: Capital Medical University
Sponsor class: OTHER
Collaborators: name: University of Oxford
name: Peking University
name: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention
First posted: 2018-12-26
Enrollment: 200
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomised, double-blind, controlled study to assess the efficacy and safety of arbidol plus oseltamivir, compared with oseltamivir alone in approximately 200 hospitalized adults and adolescent patients with confirmed severe influenza. Patients should be randomised as soon as possible after screening (no later than 12 hours), providing they are within 7 days of symptom onset. Patients will be assigned in a 1:1 ratio to receive an arbidol plus oseltamivir, or oseltamivir plus placebo. Rescreening of patients who fail to meet the inclusion and exclusion criteria will be permitted only once, providing the time from symptom onset to randomization is still within 7 days.

Arbidol/placebo will be administrated as 200mg TID from Days 1-7. Oseltamivir will be administered as 75mg twice daily from Days 1-7 (dose to be adjusted for renal impairment). Oseltamivir could be continued till influenza PCR negative. Both drugs, along with the corresponding placebo for arbidol, will be started at the time of randomization.


Eligibility criteria: Inclusion Criteria:

1. Hospitalized males or females with a positive PCR test for influenza virus infection
2. Age ≥16 years at the time of signing Informed Consent Form
3. Arterial oxygen saturation (SaO2)/ pulse oxygen saturation (SPO2) ≤94% in room air condition
4. ≤ 7 days since symptom onset. The onset of symptoms is defined as either: Time of the first increase in body temperature (an increase of at least 1ºC from normal body temperature- ≥38℃); Time when the patient experiences at least one general or respiratory symptom.
5. Willingness to use contraception for 7 days after the end of treatment

Exclusion Criteria:

1. Physicians make a decision that trial involvement is not in patients' best interest, or any condition that does not allow the protocol to be followed safely.
2. Patient refusal to accept invasive organ support treatment if needed
3. More than 3 consecutive doses of NAIs within 2 days before enrolment (including oseltamivir, zanamivir, peramivir)
4. Women who are pregnant (including a positive pregnancy test at enrolment), breastfeeding, or within 2 weeks post-partum.

   The following female subjects do not need to undergo a pregnancy test at enrolment: a. Postmenopausal (defined as cessation of regular menstrual periods for 2 years or more and confirmed by a follicle-stimulating hormone test) women. b. Women who are surgically sterile by hysterectomy, bilateral oophorectomy, or tubal ligation.
5. Any condition requiring renal replacement therapy
6. Severe liver disease (Child-Pugh score ≥ C)
7. A history of hypersensitivity to arbidol or oseltamivir (Tamiflu®)
8. Currently or have been involved in another anti-influenza treatment trial in the last 28 days
9. Patients who, in the opinion of the investigator, would be unlikely to comply with required study visits, self-assessments, and interventions

Primary outcomes:
measure: The primary efficacy endpoint was time to clinical status improvement (the event) up to 28 days
timeFrame: 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: China-Japan Friendship Hospital
state: Beijing
Study officials:
References: