{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T10:18:48Z","timestamp":1747217928956,"version":"3.40.5"},"reference-count":34,"publisher":"National Institute for Health and Care Research","issue":"43","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["15\/39\/06"],"award-info":[{"award-number":["15\/39\/06"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journalslibrary.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\">\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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 \u2265\u200918 years with this condition.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-2\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-3\">\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>This was a 66-month, definitive, multisite, two-arm, parallel-group, placebo-controlled, double-blind, randomised controlled trial, with an internal pilot phase.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-4\">\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Eight secondary care NHS hospitals across the UK.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-5\">\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>Planned trial size \u2013 280 adult patients with avascular necrosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-6\">\n                  <jats:title>Intervention<\/jats:title>\n                  <jats:p>Participants in the intervention group received 70\u2009mg of alendronate (an oral bisphosphonate) weekly for 12 months.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-7\">\n                  <jats:title>Main outcomes<\/jats:title>\n                  <jats:p>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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-8\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Twenty-one patients were recruited and randomised to receive either the intervention drug, alendronate, or a placebo-matched tablet.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-9\">\n                  <jats:title>Limitations<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-10\">\n                  <jats:title>Future work<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-11\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-12\">\n                  <jats:title>Trial registration<\/jats:title>\n                  <jats:p>The trial is registered as ISRCTN14015902.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"abs1-13\">\n                  <jats:title>Funding<\/jats:title>\n                  <jats:p>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 <jats:italic>Health Technology Assessment<\/jats:italic>; Vol. 26, No. 43. See the NIHR Journals Library website for further project information.<\/jats:p>\n               <\/jats:sec>","DOI":"10.3310\/avzv0799","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T09:19:55Z","timestamp":1667380795000},"page":"1-58","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Assessing a 12-month course of oral alendronate for adults with avascular necrosis of the hip: MANTIS RCT with internal pilot"],"prefix":"10.3310","volume":"26","clinical-trial-number":[{"clinical-trial-number":"isrctn14015902","registry":"10.18810\/isrctn","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9130-3167","authenticated-orcid":true,"given":"Sion","family":"Glyn-Jones","sequence":"first","affiliation":[{"name":"Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, 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