MANTIS
Research type
Research Study
Full title
A multi-centre, blinded, randomised, placebo-controlled trial assessing the clinical and cost effectiveness of a 12 month course of oral alendronate (70mg weekly) in patients presenting with avascular necrosis of the hip - Managing Avascular Necrosis Treatments: an Interventional Study (MANTIS)
IRAS ID
230545
Contact name
Sion Glyn-Jones
Contact email
Sponsor organisation
University of Oxford
Eudract number
2017-002798-21
Duration of Study in the UK
4 years, 7 months, 1 days
Research summary
Summary of Research
MANTIS is a blinded, multi-centre, randomised, placebo controlled clinical trial.
Patients with Avascular Necrosis (AVN) of the hip who have consented to participate will be randomised to receive either a 12 month course of oral alendronate (70mg 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.
Summary of Results
Abstract
Background: People with avascular necrosis of the hip have very limited treatment options currently available to stop the progression of this disease; this often results in the need for a hip replacement. There is some weak evidence that a class of drugs called bisphosphonates may delay the course of the disease, and this trial was commissioned and set up to provide robust evidence regarding the use of bisphosphonates in adults aged ≥ 18 years with this condition.Objectives: The aim of the Managing Avascular Necrosis Treatments: an Interventional Study ( MANTIS ) trial was to evaluate the clinical effectiveness and cost-effectiveness of a 12-month course of alendronate in the treatment of avascular necrosis.
Design: This was a 66-month, definitive, multisite, two-arm, parallel-group, placebo-controlled, double-blind, randomised controlled trial, with an internal pilot phase.
Setting: Eight secondary care NHS hospitals across the UK.
Participants: Planned trial size - 280 adult patients with avascular necrosis.
Intervention: Participants in the intervention group received 70 mg of alendronate (an oral bisphosphonate) weekly for 12 months.
Main outcomes: The main outcomes were Oxford Hip Score at 12 months (short-term outcome) and the time to decision that a hip replacement is required at 36 months (long-term outcome).
Results: Twenty-one patients were recruited and randomised to receive either the intervention drug, alendronate, or a placebo-matched tablet.
Limitations: This trial was principally limited by low disease prevalence. Other limitations included the late disease stage at which participants were identified and the rapid progression of the disease.
Future work: This trial was limited by a low recruitment rate. Avascular necrosis of the hip should be treated as a rare disease. Future trials would need to recruit many more sites and recruit over a longer time period, and, for this reason, a registry may provide a more effective means of collecting data pertaining to this disease.
Conclusions: The MANTIS trial was terminated at the end of the pilot phase, because it did not meet its go/no-go criteria. The main issue was a poor recruitment rate, owing to a lower than expected disease prevalence and difficulties in identifying the condition at a sufficiently early stage. Those patients who were identified and screened either were too advanced in their disease progression or were already taking medication. We would not recommend that a short-term interventional study is conducted on this condition until its prevalence, geographic foci and natural history and better understood. The difficulty of acquiring this understanding is likely to be a barrier in most health-care markets. One means of developing this understanding would be the introduction of a database/registry for patients suffering from avascular necrosis of the hip.
Trial registration: The trial is registered as ISRCTN14015902.
Funding: This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 43. See the NIHR Journals Library website for further project information.
REC name
South Central - Oxford A Research Ethics Committee
REC reference
18/SC/0247
Date of REC Opinion
29 May 2018
REC opinion
Further Information Favourable Opinion