Condition category
Musculoskeletal Diseases
Date applied
11/06/2018
Date assigned
12/06/2018
Last edited
12/06/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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 (70mg 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

Trial website

https://www.ndorms.ox.ac.uk/clinical-trials/current-trials-and-studies/m

Contact information

Type

Scientific

Primary contact

Miss Gemma Greenall

ORCID ID

Contact details

Surgical Intervention Trials Unit
Nuffield Department of Orthopaedics
Rheumatology & Musculoskeletal Sciences (NDORMS)
University of Oxford
Botnar Research Centre
Oxford
OX3 7LD
United Kingdom
+44 (0)1865 223665
mantis@ndorms.ox.ac.uk

Additional identifiers

EudraCT number

2017-002798-21

ClinicalTrials.gov number

Protocol/serial number

37920

Study information

Scientific 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)

Acronym

MANTIS

Study hypothesis

To assess the effect of Bisphosphonate treatment (Alendronate) on Avascular Necrosis (AVN) of the hip.

Ethics approval

South Central – Oxford A Research Ethics Committee, 29/05/2018, ref: 18/SC/0247

Study design

Randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Musculoskeletal Disorders, Primary sub-specialty: Other; UKCRC code/ Disease: Musculoskeletal/ Other osteopathies

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

Other

Phase

Phase IV

Drug names

Primary outcome measure

Hip function measured using Oxford Hip Score (OHS); Timepoint(s): 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 trial start date

01/06/2017

Overall trial end date

01/12/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Patients will be eligible for inclusion in the trial if:
1. They have early, symptomatic, atraumatic AVN of the hip (Ficat score 1 or 2 using MRI)
2. They are aged greater than or equal to 18 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 280; UK Sample Size: 280

Participant exclusion criteria

Patients will be excluded from this trial if they have/are:
1. Not confirmed their diagnosis (Ficat 1 or 2), using MRI, within the last 12 months
2. Renal function (creatinine clearance) of < 30ml/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. 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

01/12/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Nuffield Orthopaedic Centre (lead site)
Windmill Road Headington
Oxford
OX3 7HE
United Kingdom

Sponsor information

Organisation

University of Oxford

Sponsor details

Clinical Trials and Research Governance
Joint Research Office
Block 60
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
+44 (0)1865 289885
ctrg@admin.ox.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: 15/39/06

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

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 statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/12/2023

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes