Contact information
Type
Scientific
Primary contact
Prof Martin Underwood
ORCID ID
Contact details
Queen Mary's School of Medicine & Dentistry
Barts & The London
Centre for Health Sciences
Abernethy Building
2 Newark Street
Whitechapel
London
E1 2AT
United Kingdom
+44 (0)207 882 2511
m.underwood@qmul.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
HTA 01/09/02
Study information
Scientific title
Are topical or oral ibuprofen equally effective for the treatment of chronic knee pain in older people?
Acronym
TOIB
Study hypothesis
1. To ascertain, for older people with knee pain, if oral and topical ibuprofen are equally effective at reducing pain and disability in a randomised controlled trial
2. To compare the incidence of adverse effects from oral and topical ibuprofen used to treat older people with knee pain
3. To compare the cost effectiveness of oral and topical ibuprofen used for treatment of older people with knee pain
4. To compare expected and actual satisfaction with treatment, with effectiveness of oral and topical ibuprofen for older people with knee pain
5. To explore how older people's expressed preferences for, and previous use of, oral or topical medication for chronic knee pain influences treatment effectiveness
6. To explore older people's beliefs about and expectations of treatments for chronic knee pain
Ethics approval
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Knee pain
Intervention
The two interventions being compared are the GP's recommendation (either a prescription or advice to get an over-the-counter preparation) to use either topical or oral ibuprofen. For those whose chosen/allocated treatment is oral ibuprofen, practices are asked to use no more than 1.2 g per day. Treatments for knee pain other than NSAIDs may be used as each patient's doctor thinks appropriate.
Participants are sent postal questionnaires three, six, 12 and 24 months after randomisation. One year and two years after randomisation participants are asked to visit the practice to have their blood pressure and respiratory function measured and blood taken for full blood count, serum ferritin, creatinine and liver function tests. The medical records are examined one year after randomisation to identify unplanned hospital admissions, and after two years (or at the end of the study) to collect health service activity data and confirm reported changes in medication and adverse effects.
Intervention type
Drug
Phase
Not Specified
Drug names
Ibuprofen
Primary outcome measures
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, which measures pain and disability in the preceding 48 hours.
Secondary outcome measures
1. The postal version of the Chronic Pain Grade, which measures pain and disability over the preceding six months
2. The Euro Quality of Life questionnaire (EQ-5D), a measure of health-related quality of life
3. The 36-item Short Form health survey (SF-36) version 2, a different measure of health related quality of life
4. A question assessing satisfaction with treatment
Overall trial start date
01/07/2002
Overall trial end date
31/08/2006
Reason abandoned
Eligibility
Participant inclusion criteria
1. Aged 50 or over
2. Have ever had pain in or around the knee on most days for at least a month and have experienced knee pain for more than three months out of the preceding year
3. General Practitioner (GP) consultation, or treatment, for knee pain in the preceding three years
4. Informed consent
5. Agreement to use chosen or allocated treatment
6. GP agreement to prescribe oral/topical ibuprofen
7. Ability to complete postal questionnaires
Participant type
Patient
Age group
Senior
Gender
Both
Target number of participants
283
Participant exclusion criteria
1. Peptic ulceration (past or current)
2. Current moderate or severe indigestion
3. Previous severe adverse reaction to Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
4. Hypertension (systolic Blood Pressure [BP] of 155 mmHg or more or a diastolic BP of 105 mmHg or more)
5. Uncontrolled heart failure
6. Creatinine greater than 140 mmol/L
7. Abnormal liver function sufficient to contraindicate use of NSAIDs (as liver function tests performed and reference ranges vary between different laboratories, this decision is at the discretion of the participant's GP)
8. GP request not to include
9. Serious psychological or psychiatric disorders (including dementia)
10. Previous knee replacement/s or awaiting knee surgery
11. Inflammatory arthropathy
12. Pain referred from hip or back
13. Serious injury within six months
14. Currently on anticoagulants or oral steroids
15. Anaemia (Haemoglobin [Hb] less than 12.4 g/L for men or less than 11.8 g/L for women)
16. Disseminated malignancy
To meet the American College of Rheumatologists (ACR) clinical criteria for osteoarthritis of the knee, patients need to have knee pain, as defined for this study, and meet three out of the following six criteria:
1. Aged over fifty
2. Less than 30 minutes morning stiffness
3. Crepitus
4. Bony tenderness
5. Bony enlargement
6. No palpable warmth
Recruitment start date
01/07/2002
Recruitment end date
31/08/2006
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Queen Mary's School of Medicine & Dentistry
London
E1 2AT
United Kingdom
Sponsor information
Organisation
Department of Health (UK)
Sponsor details
Quarry House
Quarry Hill
Leeds
LS2 7UE
United Kingdom
+44 (0)1132 545 843
Sheila.Greener@doh.gsi.gov.uk
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
NIHR Health Technology Assessment Programme - HTA (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2008 cost-effectiveness results in http://www.ncbi.nlm.nih.gov/pubmed/18511476
2008 HTA monograph at http://www.ncbi.nlm.nih.gov/pubmed/18505668
2008 main results publication at http://www.ncbi.nlm.nih.gov/pubmed/18056743
2005 protocol in http://www.ncbi.nlm.nih.gov/pubmed/16274477
Publication citations
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Protocol
Cross PL, Ashby D, Harding G, Hennessy EM, Letley L, Parsons S, Spencer AE, Underwood M, , TOIB Study. Are topical or oral ibuprofen equally effective for the treatment of chronic knee pain presenting in primary care: a randomised controlled trial with patient preference study. [ISRCTN79353052]., BMC Musculoskelet Disord, 2005, 6, 55, doi: 10.1186/1471-2474-6-55.
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Castelnuovo E, Cross P, Mt-Isa S, Spencer A, Underwood M, , Cost-effectiveness of advising the use of topical or oral ibuprofen for knee pain; the TOIB study [ISRCTN: 79353052]., Rheumatology (Oxford), 2008, 47, 7, 1077-1081, doi: 10.1093/rheumatology/ken128.
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Underwood M, Ashby D, Carnes D, Castelnuovo E, Cross P, Harding G, Hennessy E, Letley L, Martin J, Mt-Isa S, Parsons S, Spencer A, Vickers M, Whyte K, Topical or oral ibuprofen for chronic knee pain in older people. The TOIB study., Health Technol Assess, 2008, 12, 22, iii-iv, ix-155.
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Underwood M, Ashby D, Cross P, Hennessy E, Letley L, Martin J, Mt-Isa S, Parsons S, Vickers M, Whyte K, , Advice to use topical or oral ibuprofen for chronic knee pain in older people: randomised controlled trial and patient preference study., BMJ, 2008, 336, 7636, 138-142, doi: 10.1136/bmj.39399.656331.25.