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] - Injuries, poisonings, and occupational diseases [C21] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017076 |
E.1.2 | Term | Fracture |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
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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 |
The aim of the study is to determine if alendronic acid - the drug most commonly used in the UK as treatment of osteoporosis (thinning bones) - affects fracture healing. Participants will be randomised to receive either alendronic acid or a placebo (a tablet that contains no active drug).
The main objective will be to look at the x-rays that are taken 4 weeks into the study and compare the number of healed fractures in each group (alendronic acid or placebo). We will also look at how long it takes a fracture to heal, using the x-rays taken at weeks 2, 4, 6 and 8.
One person will analyse all the x-rays in the study. The x-rays will be anonymised so that the reviewer is unaware of individual details or the treatment that the participant received. |
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E.2.2 | Secondary objectives of the trial |
We will also look at the outcomes of wrist fracture such as how well the wrist is working and the patient's pain.
Wrist function will be compared between both groups using the Disabilities of the Arm, Shoulder and Hand (DASH) Outcome measure. This is a 30 item questionnaire.
Wrist function will also be measured by comparing the range of movement (i.e. flexibility) of a participant's wrist joint.
The amount of pain a participant is in and the amount pain medication used will be compared between both groups.
The grip strength of participants will be compared between both groups.
Malunion (where the bone does not join up properly) of the fracture site will be assessed by X-ray at week 26. The presence and frequency of malunion will be compared between each group.
Participants will also be assessed for Complex Regional Pain Syndrome type I (CRPS-I). This is a condition that can happen after a fracture and involves abnormal pain levels and other symptoms such as reduced |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Full Title: Fractures and Bisphosphonates: A double-blind, randomised controlled trial on the effect of alendronic acid on healing and clinical outcomes of wrist fractures - HIGH RESOLUTION PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY (HR-pQCT) SUB-STUDY.
Protocol Version & Date: 1.1, 6th July 2011
Primary Objective: To determine the effect of alendronic acid on total volumetric bone density measured by HR-pQCT during radial fracture healing. |
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E.3 | Principal inclusion criteria |
1. Patients (male and female) aged 50 years and over 2. Patients must have suffered a distal radial fracture confirmed by X-ray radiograph. 3. The distal radial fracture must be: i) unilateral extra-articular or minimal articular ii) displaced or un-displaced iii) treated with cast/splint, external fixation or open reduction and internal fixation. 4. Patients willing and able to consent and comply with study protocol.
For the HR-pQCT substudy, participants must also satisfy the following criteria: - a stabilized fracture using a plaster cast (with or without manipulation) - proximal extent of the fracture site must be within 2 cm of the lunate fossa - willing to undergo HR-pQCT scans of the wrist, at four of the main study visits, and incur a small additional exposure to ionizing radiation.
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E.4 | Principal exclusion criteria |
1. Any of the following: i) current or previous use of zoledronic acid ii) current or previous use within the last 2 years of any other bisphosphonate. iii) current or previous use within the last 6 months of strontium ranelate, calcitonin, Denosumab, parathyroid hormone (PTH) or IV, IM and oral corticosteroids (inhaled corticosteroids such as asthma inhalers are acceptable). 2. Previous distal radial fracture on affected side. 3. Bilateral distal radial fracture. 4. Contraindications to alendronic acid, including but not limited to: i) abnormalities of the oesophagus and other factors which delay oesophageal emptying such as stricture or achlasia ii) inability to stand or sit upright for at least 30 minutes iii) hypersensitivity to alendronate or any of its excipients iv) known hypocalcaemia v) known renal impairment 5. Women of child bearing potential not using adequate contraception. 6. Pregnancy. 7. The distal radial fracture is due to other pathologies e.g. Paget’s Disease of Bone, metastatic bone disease etc.
For the HR-pQCT substudy, the following exclusion criteria also apply: - Unable or unwilling to provide informed consent for participation in the sub-study - Treatment of the fracture which involves the insertion of metal implants (e.g. wires, fixators or plate/screws) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary analysis will be measured by comparing the percentage of fractures healed in each treatment group (alendronic acid vs placebo) at 4 weeks.
The study is designed and powered to allow a definitive comparison of fracture healing rates after 4 weeks of treatment. Since previous studies have yielded conflicting results we have also ensured that the study is adequately powered to perform a non-inferiority comparison assuming that fracture healing time with alendronate will be similar to that of placebo to within four days. The difference between groups will be assessed by comparing the proportion of participants whose fracture has healed by week 4 in each treatment group. However a time to event analysis will also be performed to evaluate the trajectory of fracture healing from radiographs taken at 2, 4, 6 and 8 weeks.
Fractures will be defined as healed when the following features are present: 1. Bridging of three out of four cortices 2. Radiographic evidence of endosteal healing 3. Organised trabecular bridging |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The endpoint will be measured at 4 weeks, with also an analysis of the trajectory of fracture healing from the radiographs taken at 2, 4, 6 and 8 weeks. |
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E.5.2 | Secondary end point(s) |
1. The effect of alendronate on the DASH score during the trial will be measured by compared in both treatment groups. 2. The presence of Complex Regional Pain Syndrome type I (CRPS-I) will be assessed compared between both treatment groups. 3. The difference in pain and analgesia use will be compared between both treatment groups. 4. The differences between the range of movement in each hand will be used to compare the two treatment groups. 5. The difference in grip strength between each hand will be used to compare the two treatment groups. 6. The presence of malunion will be compared between both treatment groups. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. The DASH score will be assessed at baseline, weeks 2, 4, 6, 8 and 26 2. CRPS-I will be evaluated at week 6 and 26. 3. Pain and analgesia use will be evaluated at baseline, weeks 2, 4, 6, 8 and 26 4. Range of movement will be assessed at weeks 8 and 26. 5. Grip strength will be assessed at weeks 8 and 26. 6. Malunion will be assessed by radiograph at week 26. |
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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 | No |
E.6.4 | Safety | Yes |
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 | Yes |
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 | 7 |
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 | Yes |
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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End of trial is the last participant's last study visit. (LVLS) |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |