The Benefit and Harm of Fever Suppression by Antipyretics in Influenza

NCT ID: NCT01891084

Last Updated: 2019-01-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-07-31

Study Completion Date

2018-12-31

Brief Summary

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The purpose of this study is to investigate the potential benefits and risks of antipyretics use in naturally occurring influenza virus infections in humans.

Detailed Description

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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:

To investigate the potential benefits and risks of antipyretic use in naturally occurring influenza virus infections in humans.

Design and subjects:

The study is a double-blind, randomized controlled trial. Four hundred young adults aged 18-30 years will be recruited when they present with symptoms of acute respiratory infection within 48 hours of symptoms onset to university health clinics, and being tested positive with a QuickVue rapid influenza test. They will receive their clinical consultation and prescriptions as indicated as usual, and being randomized to receive either paracetamol or placebo, and given back-up NSAID for intolerable fever when required. Blood specimen, nasal and throat swabs will be collected on the same day (day 1). They will be followed-up on day 4, day 7 and day 10 for further collection of nasal and throat swabs, and on day 28 for a final blood taking. A symptom diary will be kept by each participant for 10 days for monitoring the clinical course of the infection.

Potential significance:

This will be the first RCT to investigate the effect of antipyretics on the clinical course, disease duration, and the pattern of viral shedding in naturally occurring influenza virus infection in humans. Findings from this study will have important contribution to our understanding on the role of fever as a host defense mechanism, and help to inform the appropriate clinical management approach in human influenza virus infection.

Conditions

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Influenza

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Paracetamol

Intervention Type DRUG

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.

Backup NSAID ibuprofen

Intervention Type DRUG

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.

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

(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.

Backup NSAID ibuprofen

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Backup NSAID ibuprofen

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.

Intervention Type DRUG

Other Intervention Names

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Acetaminophen ibuprofen

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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The University of Hong Kong

OTHER

Sponsor Role lead

Responsible Party

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Dr. Dennis Kai-Ming Ip

Clinical Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Dennis KM Ip, MBBS

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

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University Health Service, The Hong Kong Polytechnic University

Hong Kong, Hksar, , China

Site Status

Countries

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China

Other Identifiers

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DKMI003.4

Identifier Type: -

Identifier Source: org_study_id

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