A Randomized Controlled Trial on the Effect of Fever Suppression by Antipyretics on Influenza
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Time from recruitment to illness resolution, defined as the time when fever and at least nine out of the ten influenza symptoms had subsided (graded as 0 by the patient) for a period of 24 hours.
研究概览
简要总结
The purpose of this study is to investigate the potential benefits and risks of antipyretics use in naturally occurring influenza virus infections in humans.
详细描述
Background:
Being one of the commonest conditions encountered in modern medical practice, fever is commonly regarded as an illness that has to be treated, both by medical professionals and patients. However, objective and convincing evidence is lacking that naturally occurring fever is harmful, and there is growing evidence that fever may serve an important host defense mechanism in infections and the risks of its suppression may far outweigh its apparent benefits. In acute respiratory infections including influenza, antipyretics are commonly being prescribed as a symptomatic treatment. Evidence from different randomized controlled trials, however, had challenged the actual amount of clinical benefit achievable by fever suppression for improving the patients' comfort and behavior. On the other hand, evidence from animal and human challenge studies has suggested that antipyretic therapy may actually prolong the duration of illness, suppress humoral antibody response, and increase the level and duration of viral shedding.
The knowledge gap:
Most of the currently available evidence on the harms and benefits of antipyretic treatment of upper respiratory tract infections (URTIs) are from either experimental animal studies, or human challenge studies with various respiratory viruses, or from randomized controlled trials (RCTs) on patients with fever of presumed viral origin. There has yet been no RCT that has investigated on the effect of antipyretics on the clinical course, disease duration, and the pattern of viral shedding in naturally occurring acute URTIs of viral origin in humans. Whereas acute URTIs can be caused by a range of viral and non-viral causes, influenza virus infection is one of its leading cause, and its pathogenesis is relatively well understood compared to some other respiratory viruses.
Aim:
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
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 30 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults aged between 18-30
- •Presenting with symptoms of acute URTI (at least two among the following symptoms: body temperature ≥37.8°C, cough, rhinorrhea, sore throat, headache, myalgia/arthralgia) within 48 hours of illness onset
- •being tested positive with a QuickVue rapid influenza test
排除标准
- •Allergic to paracetamol or any other antipyretics
- •Have any underlying immunocompromized condition or be receiving immunosuppressive agents.
- •Have any history of chronic liver disease, or any active lung, heart or renal diseases requiring regular medication.
研究组 & 干预措施
Paracetamol
Paracetamol 1 tablet (500mg) four times daily. For a maximum period of 5 days if the patient is still having fever. When required, participants may take up to 2 tablets (1gm) in each dose. Precautionary statement (Do not exceed 8 tablets daily) will be printed on the dispensary label to avoid overdose.
Backup NSAID ibuprofen 200mg orally every 8 hourly will also be provided to all participants, which can be taken when necessary (PRN) if the participant finds the fever intolerable.
干预措施: Paracetamol (Drug)
Paracetamol
Paracetamol 1 tablet (500mg) four times daily. For a maximum period of 5 days if the patient is still having fever. When required, participants may take up to 2 tablets (1gm) in each dose. Precautionary statement (Do not exceed 8 tablets daily) will be printed on the dispensary label to avoid overdose.
Backup NSAID ibuprofen 200mg orally every 8 hourly will also be provided to all participants, which can be taken when necessary (PRN) if the participant finds the fever intolerable.
干预措施: Backup NSAID ibuprofen (Drug)
Placebo
(Identical-looking) Placebo 1 tablet four times daily. For a maximum period of 5 days if the patient is still having fever. When required, participants may take up to 2 tablets in each dose. Precautionary statement (Do not exceed 8 tablets daily) will be printed on the dispensary label to avoid overdose.
Backup NSAID ibuprofen 200mg orally every 8 hourly will also be provided to all participants, which can be taken when necessary (PRN) if the participant finds the fever intolerable
干预措施: Placebo (Drug)
Placebo
(Identical-looking) Placebo 1 tablet four times daily. For a maximum period of 5 days if the patient is still having fever. When required, participants may take up to 2 tablets in each dose. Precautionary statement (Do not exceed 8 tablets daily) will be printed on the dispensary label to avoid overdose.
Backup NSAID ibuprofen 200mg orally every 8 hourly will also be provided to all participants, which can be taken when necessary (PRN) if the participant finds the fever intolerable
干预措施: Backup NSAID ibuprofen (Drug)
结局指标
主要结局
Time from recruitment to illness resolution, defined as the time when fever and at least nine out of the ten influenza symptoms had subsided (graded as 0 by the patient) for a period of 24 hours.
时间窗: 10 days
Self-recording of temperature twice daily for ten days (D1-D10) will be performed and recorded using a standard tympanic thermometer provided for free to each participant. Participants will also keep symptom diary twice daily for 10 days (from D1-D10), using 4-point scale of 0, 1, 2, or 3 for absent, mild, moderate, or severe symptoms respectively. Mild symptoms are easily tolerated and do not interfere with any usual activities; moderate symptoms interfere with usual activities; Severe symptoms are such that the individual cannot carry out usual activities. Ten common influenza symptoms (including feverishness, chills, cough, rhinorrhea, sore throat, general fatigue, headache, myalgia/arthralgia, vomiting, and diarrhea) will be recorded.
Time from recruitment to cessation of viral shedding, defined as the time when no virus is detected by RT-PCR from both nasal and throat swabs.
时间窗: 10 days
Nasal and throat swabs will be collected on D1, D4, D7 and D10 for viral identification and subtyping by viral culture, and viral load detection and quantification by quantitative RT-PCR.
次要结局
- The duration of individual symptoms(10 days)
- Time to cessation of illness and viral shedding from illness onset(10 days)
- Quality of life(10 days)
- The incidence of secondary complications(10 days)
- The use of backup NSAID provided(10 days)
- The severity of individual symptoms(10 days)
- Geometric mean rise in antibody titre against the infecting type or subtype of influenza virus(28 days)
研究者
Dr. Dennis Kai-Ming Ip
Clinical Assistant Professor
The University of Hong Kong