Severe Influenza Trial of ARbidol (STAR)

Oseltamivir and Arbidol Combination Antiviral Therapy Versus Oseltamivir Monotherapy for the Treatment of Severe influenza: a Multicentre, Double-blind, Randomised Phase 3 Trial

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.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Drug: Placebos; Drug: Arbidol

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100029
      • China-Japan Friendship Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Hospitalized males or females with a positive antigen or 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: oseltamivir plus placebo	Drug: Placebos; Oseltamivir plus placebos will be administrated from Days 1-7.
Experimental: oseltamivir plus arbidol	Drug: Arbidol; Oseltamivir plus Arbidol will be administrated from Days 1-7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary efficacy endpoint was time to clinical status improvement (the event) up to 28 days	the event defined as seven-category ordinal scale of clinical status after enrolment decrease by two category or discharged	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to decline of one category on the seven-category ordinal scale of clinical status lasting for 48h, or hospital discharge within 28 days, days	the event defined as seven-category ordinal scale of clinical status after enrolment decrease by one category or discharged	Up to 28 days
Day 28 mortality rate		28 days
Proportion of Clinical Improvement (≥2-category decline / discharge with improvement) at Days 7, 14, and 28 since arbidol initiation		Up to 28 days
Proportion of Patients at Each Category of the 7-category Ordinal Scale at Days 7, 14, and 28		up to 28 days
Duration of Mechanical Ventilation (days), Oxygen Therapy (days), Hospitalization (days), Time from Randomization to Discharge (days), Time from Randomization to Death (days)		Up to 28 days
Incidence of Secondary Infection, Secondary Aspergillus and Bacterial Infection		Up to 28 days
Patients Requiring Continuous Renal Replacement Therapy (CRRT) After Treatment		Up to 28 days

Collaborators and Investigators

• Sponsor: Capital Medical University
• Collaborators: Peking University; University of Oxford; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2019
• Primary Completion (Actual): April 9, 2023
• Study Completion (Actual): October 17, 2024

Study Registration Dates

• First Submitted: December 22, 2018
• First Submitted That Met QC Criteria: December 22, 2018
• First Posted (Actual): December 26, 2018

Study Record Updates

• Last Update Posted (Estimated): June 25, 2025
• Last Update Submitted That Met QC Criteria: June 19, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: severe influenza, arbidol, oseltamivir, ordinal scale
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human
• Other Study ID Numbers: CAP-China Arbidol

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Dear Sir/Madam Our study receives a grant from China Ministry of Science and Technology. We cannot decide whether the data could be shared. Hope you can understand.

Best

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No