E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023476 |
E.1.2 | Term | Knee osteoarthritis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This pilot study’s purpose it to provide preliminary evidence on which to base sample size calculations for a possible future trial which will answer the question: “Is spironolactone more effective than placebo in reducing knee pain in older people with symptomatic osteoarthritis (OA) of the knee, when given in addition to usual analgesia?” |
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E.2.2 | Secondary objectives of the trial |
To obtain preliminary evidence and data on whether oral spironolactone therapy improves health-related quality of life compared to placebo in older people with knee OA.
To measure blood tests to provide scientific evidence to inform interpretation of the study finding.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a. Participant is willing and able to give informed consent. b. Community dwelling c. Aged 70 years and over d. Symptomatic idiopathic OA knee according to American College of Rheumatology clinical and radiographic criteria (ie Knee pain - with or without crepitus - and presence of osteophytes on x ray) e. To avoid floor effects, participants will require to have moderate (or more severe) pain at baseline in at least 2 out of 5 WOMAC pain score items f. To have been in receipt of one or more analgesic agents at a therapeutic dose for at least 2 months g. Willing to have knee x-ray if one has not been taken in preceding 12 months
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E.4 | Principal exclusion criteria |
a. Clinical diagnosis of symptomatic heart failure b. History of inflammatory arthritis c. Already taking spironolactone d. Previous intolerance to spironolactone e. Known allergies to spironolactone or lactose f. Objection to taking capsules made from animal sourced gelatine g. Taking oral NSAIDs (because of the increased risk of renal impairment when combined with spironolactone) h. Taking ACE inhibitors or ARBs (angiotensin II receptor antagonists). ARBs have many properties similar to those of ACE inhibitors. Both will be exclusion because of the increased risk of acute kidney injury and hyperkalaemia, and because our previous study also excluded those on ACE inhibitors (and ARBs) and treatment was safe and well tolerated. i. Supine hypotension (supine systolic blood pressure <100mmHg at screening) j. Significant chronic kidney disease (eGFR<40ml/min) k. Serum sodium<130mmol/l l. Serum potassium>5.0mmol/l m. Symptomatic orthostatic hypotension (measured at screening) n. Nursing home resident o. Wheelchair bound p. Participating in another clinical trial (other than observational trials and registries) concurrently or within 30 days prior to screening for entry into this study q. Known contraindication to spironolactone therapy r. Participant who is terminally ill, defined as less than 3 months expected survival
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E.5 End points |
E.5.1 | Primary end point(s) |
Between group difference in change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (5 items) at 12 weeks |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Between group difference in change in WOMAC stiffness subscale
Between group difference in change in WOMAC physical function subscales
Between group difference in change in health-related quality of life measured by EQ-5D questionnaire
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Completion of all trial assessments by the LVLS. However the data analysis will be conducted after that and the whole study duration is expected to last 1 year and 6 months including analysis. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 30 |