Oseltamivir and Arbidol Combination Antiviral Therapy Versus Oseltamivir Monotherapy for the Treatment of Severe influenza: a Multicentre, Double-blind, Randomised Phase 3 Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- The primary efficacy endpoint was time to clinical status improvement (the event) up to 28 days
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hospitalized males or females with a positive antigen or PCR test for influenza virus infection
- •Age ≥16 years at the time of signing Informed Consent Form
- •Arterial oxygen saturation (SaO2)/ pulse oxygen saturation (SPO2) ≤94% in room air condition
- •≤ 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.
- •Willingness to use contraception for 7 days after the end of treatment
排除标准
- •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.
- •Patient refusal to accept invasive organ support treatment if needed
- •More than 3 consecutive doses of NAIs within 2 days before enrolment (including oseltamivir, zanamivir, peramivir)
- •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.
- •Any condition requiring renal replacement therapy
- •Severe liver disease (Child-Pugh score ≥ C)
- •A history of hypersensitivity to arbidol or oseltamivir (Tamiflu®)
- •Currently or have been involved in another anti-influenza treatment trial in the last 28 days
- •Patients who, in the opinion of the investigator, would be unlikely to comply with required study visits, self-assessments, and interventions
研究组 & 干预措施
oseltamivir plus arbidol
干预措施: Arbidol (Drug)
oseltamivir plus placebo
干预措施: Placebos (Drug)
结局指标
主要结局
The primary efficacy endpoint was time to clinical status improvement (the event) up to 28 days
时间窗: 28 days
the event defined as seven-category ordinal scale of clinical status after enrolment decrease by two category or discharged
次要结局
- 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(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)
研究者
Bin Cao
China-Japan Friendship Hospital
Capital Medical University