Managing Avascular Necrosis Treatments: an Investigational Study (MANTIS)
| ISRCTN | ISRCTN14015902 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14015902 |
| EudraCT/CTIS number | 2017-002798-21 |
| Secondary identifying numbers | 37920 |
- Submission date
- 11/06/2018
- Registration date
- 12/06/2018
- Last edited
- 03/11/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Plain English Summary
Background and study aims
Avascular necrosis (AVN) is death of bone tissue due to interruption of the blood supply. The aim of this study is to assess the effect of a bisphosphonate drug treatment (Alendronate) on AVN of the hip.
Who can participate?
Patients aged 18 and over with AVN of the hip
What does the study involve?
Participants are randomly allocated to receive either a 12 month course of oral alendronate (70 mg taken weekly), or a matched placebo (dummy drug). This is in addition to standard care for the condition which includes non-weight bearing periods and over the counter pain medication. Participants are followed up for 3 years with follow-up assessments at 6, 12, 24 and 36 months and compliance assessments at 1, 2, 3, 6, 9 and 12 months: patients complete these assessments via questionnaires either in a paper format or through a secure online portal (the electronic data capture is planned to improve completion rates for the younger and more geographically mobile population). An x-ray is taken at 1 year and 3 years as part of standard routine care of patients with AVN, and the notes and images from these scans are collected. Those that haven’t had any surgery also have an MRI scan at 3 years of which the images and notes are collected. The study includes a pilot study, which progresses to the definitive trial if predefined criteria regarding recruitment are met. In the initial pilot study, a minimum of 50 patients are randomly allocated over 12 months from at least 10 sites, with a target recruitment rate of 1-2 patients per site per month. AVN is an uncommon condition, therefore the aim of the pilot study is to maximise recruitment, and ensure that outcomes can be collected reliably and remotely in all patients. It will also provide information on site feasibility.
What are the possible benefits and risks of participating?
The results of this study will improve understanding of how Alendronate works which may help to improve the treatment for future patients with AVN. Alendronate is routinely used as osteoporosis treatment and therefore has a highly reviewed safety profile. As with any medication there are risks involved and recent evidence indicates the following side effects occurred in less than 10% of patients: headache, dizziness, vertigo, abdominal pain, indigestion, constipation, diarrhoea, abdominal swelling, acid reflux, alopecia, itching, joint swelling, physical weakness or lack of energy and a build-up of fluid. Bone, muscle or joint pain is also a very common side effect occurring in more than 1 in 10 patients. There is limited information available regarding the effect of alendronate on pregnancy therefore highly effective contraceptive methods are required for all participants (regardless of sex or gender) for the duration of the study treatment and for a year after completing the treatment.
Where is the study run from?
Nuffield Orthopaedic Centre (UK)
When is the study starting and how long is it expected to run for?
June 2017 to December 2022
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
Miss Gemma Greenall
mantis@ndorms.ox.ac.uk
Contact information
Scientific
Surgical Intervention Trials Unit
Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences (NDORMS)
University of Oxford
Botnar Research Centre
Oxford
OX3 7LD
United Kingdom
| Phone | +44 (0)1865 223665 |
|---|---|
| mantis@ndorms.ox.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment, Drug |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A multi-centre, blinded, randomised, placebo-controlled trial assessing the clinical and cost effectiveness of a 12 month course of oral alendronate (70 mg weekly) in patients presenting with avascular necrosis of the hip - Managing Avascular Necrosis Treatments: an Interventional Study (MANTIS) |
| Study acronym | MANTIS |
| Study hypothesis | To assess the effect of bisphosphonate treatment (alendronate) on avascular necrosis (AVN) of the hip. |
| Ethics approval(s) | South Central – Oxford A Research Ethics Committee, 29/05/2018, ref: 18/SC/0247 |
| Condition | Avascular necrosis of the hip |
| Intervention | Randomisation will be performed using a minimisation algorithm including random elements to ensure balanced allocation of participants across the two treatment groups stratified by: 1. Randomising site 2. FICAT stage (1 or 2) 3. Main AVN risk factors (steroid/alcohol/other) obtained from clinical notes 4. Bilateral vs unilateral AVN Patients will be randomised on a 1:1 basis to receive either a 12 month course of oral alendronate (one 70mg tablet taken weekly), or a matched placebo. This will be in addition to standard care for the condition which includes non-weight bearing periods and over the counter pain medication. Patients, clinicians and assessors will be blinded to the treatment allocation. Patients will be followed up for 3 years with follow up assessments at 6, 12, 24 and 36 months and compliance assessments at 1, 2, 3, 6, 9 and 12 months: patients will complete these assessments via questionnaires either in a paper format or through a secure online portal (the electronic data capture is planned to improve completion rates for the younger and more geographically mobile population). An x-ray will be collected at 1 year and 3 years as part of standard routine care of patients with AVN, and the notes and images from these scans will be collected. Those that haven’t had any surgery will also have an MRI scan at 3 years of which the images and notes will be collected. The study will include a pilot study, which will progress to the definitive trial if predefined criteria regarding recruitment are met. In the initial pilot study, a minimum of 50 patients will be randomised over 12 months from at least 10 sites, with a target recruitment rate of 1-2 patients per site per month. AVN is an uncommon condition, therefore the aim of the pilot study is to maximise recruitment, and ensure that outcomes can be collected reliably and remotely in all patients. It will also provide information on site feasibility. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Alendronate |
| Primary outcome measure | Hip function measured using Oxford Hip Score (OHS) at 12 months |
| Secondary outcome measures | 1. Hip function and quality of life (QoL) measured using Oxford Hip Score (OHS), iHOT-33, Hospital Anxiety and Depression Score (HADS) and EQ-5D-5L at baseline, 6, 12, 24 and 36 months 2. Radiological progression measured using x-ray at 12 and 36 months and MRI at 36 months 3. Treatment compliance measured using bespoke compliance questionnaires at 1, 2, 3, 6, 9, and 12 months 4. Cost effectiveness measured using healthcare resource use questionnaires at 6, 12, 24 and 36 months |
| Overall study start date | 01/06/2017 |
| Overall study end date | 31/08/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 280; UK Sample Size: 280 |
| Total final enrolment | 21 |
| Participant inclusion criteria | 1. Early, symptomatic, atraumatic AVN of the hip (Ficat score 1 or 2 using MRI) 2. Aged 18 years or over |
| Participant exclusion criteria | 1. Diagnosis not confirmed their diagnosis (Ficat 1 or 2), using MRI, within the last 12 months 2. Renal function (creatinine clearance) of < 30 ml/min (tested within the last 3 months) 3. Adjusted serum calcium levels outside local reference range (tested within the last 3 months) 4. Established osteoarthritis (Kellgren-Lawrence >=2) 5. Previous AVN, femoral head deformity, prior hip surgery or hip fracture in the index hip 6. Current pathology (e.g. osteoporosis) that requires treatment with bisphosphonates 7. Received previous anti-osteoporosis therapy (excluding calcium or vitamin D supplements) that lasted more than 4 weeks for oral treatment or any length of parenteral treatment 8. Contraindications to MRI 9. Contraindications to alendronate therapy (including hypocalcaemia) as listed in the SmPC 10. Planning a pregnancy in the next 12 months or are currently pregnant or breastfeeding 11. Not using appropriate contraception and of child bearing age 12. Have a planned joint preserving surgical procedure of the hip 13. Unable to provide informed consent 14. Unable to commit to follow-up regime 15. Already enrolled in an interventional clinical trial |
| Recruitment start date | 15/07/2018 |
| Recruitment end date | 17/11/2019 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Headington
Oxford
OX3 7HE
United Kingdom
Sponsor information
University/education
Clinical Trials and Research Governance
Joint Research Office
Block 60
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
England
United Kingdom
| Phone | +44 (0)1865 289885 |
|---|---|
| ctrg@admin.ox.ac.uk | |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 01/08/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Results of this trial will be submitted for publication in a peer‐reviewed journal. All presentations and publications will be pre‐agreed by the Trial Steering Committee (TSC). |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 01/10/2022 | 03/11/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
03/11/2022: Publication reference added.
29/09/2020: The following changes have been made:
1. The recruitment end date has been changed from 01/12/2020 to 17/11/2019.
2. The overall trial end date has been changed from 01/12/2022 to 31/08/2020.
3. The intention to publish date has been changed from 01/12/2023 to 01/08/2021.
4. The final enrolment number has been added.
22/03/2019: The condition was updated from "Specialty: Musculoskeletal Disorders, Primary sub-specialty: Other; UKCRC code/ Disease: Musculoskeletal/ Other osteopathies" to "Avascular necrosis of the hip" following a request from the NIHR.
