This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full programme and will be published in full in Vol. 22, No. 28. See the NIHR Journals Library website for further project information. Additional funding was provided by the Oxford NIHR Biomedical Research Centre and the Oxford NIHR Collaboration for Leadership in Applied Health Research and Care.

An amendment to this paper has been published and can be accessed via the original article.

ImportanceOpioid use for chronic nonmalignant pain can be harmful.ObjectiveTo test whether a multicomponent, group-based, self-management intervention reduced opioid use and improved pain-related disability compared with usual care.Design, Setting, and ParticipantsMulticentered, randomized clinical trial of 608 adults taking strong opioids (buprenorphine, dipipanone, morphine, diamorphine, fentanyl, hydromorphone, methadone, oxycodone, papaveretum, pentazocine, pethidine, tapentadol, and tramadol) to treat chronic nonmalignant pain. The study was conducted in 191 primary care centers in England between May 17, 2017, and January 30, 2019. Final follow-up occurred March 18, 2020.InterventionParticipants were randomized 1:1 to either usual care or 3-day–long group sessions that emphasized skill-based learning and education, supplemented by 1-on-1 support delivered by a nurse and lay person for 12 months.Main Outcomes and MeasuresThe 2 primary outcomes were Patient-Reported Outcomes Measurement Information System Pain Interference Short Form 8a (PROMIS-PI-SF-8a) score (T-score range, 40.7-77; 77 indicates worst pain interference; minimal clinically important difference, 3.5) and the proportion of participants who discontinued opioids at 12 months, measured by self-report.ResultsOf 608 participants randomized (mean age, 61 years; 362 female [60%]; median daily morphine equivalent dose, 46 mg [IQR, 25 to 79]), 440 (72%) completed 12-month follow-up. There was no statistically significant difference in PROMIS-PI-SF-8a scores between the 2 groups at 12-month follow-up (−4.1 in the intervention and −3.17 in the usual care groups; between-group difference: mean difference, −0.52 [95% CI, −1.94 to 0.89]; P = .15). At 12 months, opioid discontinuation occurred in 65 of 225 participants (29%) in the intervention group and 15 of 208 participants (7%) in the usual care group (odds ratio, 5.55 [95% CI, 2.80 to 10.99]; absolute difference, 21.7% [95% CI, 14.8% to 28.6%]; P < .001). Serious adverse events occurred in 8% (25/305) of the participants in the intervention group and 5% (16/303) of the participants in the usual care group. The most common serious adverse events were gastrointestinal (2% in the intervention group and 0% in the usual care group) and locomotor/musculoskeletal (2% in the intervention group and 1% in the usual care group). Four people (1%) in the intervention group received additional medical care for possible or probable symptoms of opioid withdrawal (shortness of breath, hot flushes, fever and pain, small intestinal bleed, and an overdose suicide attempt).Conclusions and RelevanceIn people with chronic pain due to nonmalignant causes, compared with usual care, a group-based educational intervention that included group and individual support and skill-based learning significantly reduced patient-reported use of opioids, but had no effect on perceived pain interference with daily life activities.Trial Registrationisrctn.org Identifier: ISRCTN49470934

Objectives The primary objective is to determine which of two interventions: 1) an eight week, online, home-based, supervised, group rehabilitation programme (REGAIN); or 2) a single online session of advice (best-practice usual care); is the most clinically and cost-effective treatment for people with ongoing COVID-19 sequelae more than three months after hospital discharge. Trial design Multi-centre, 2-arm (1:1 ratio) parallel group, randomised controlled trial with embedded process evaluation and health economic evaluation. Participants Adults with ongoing COVID-19 sequelae more than three months after hospital discharge Inclusion criteria: 1) Adults ≥18 years; 2) ≥ 3 months after any hospital discharge related to COVID-19 infection, regardless of need for critical care or ventilatory support; 3) substantial (as defined by the participant) COVID-19 related physical and/or mental health problems; 4) access to, and able/supported to use email and internet audio/video; 4) able to provide informed consent; 5) able to understand spoken and written English, Bengali, Gujarati, Urdu, Punjabi or Mandarin, themselves or supported by family/friends. Exclusion criteria: 1) exercise contraindicated; 2) severe mental health problems preventing engagement; 3) previous randomisation in the present study; 4) already engaged in, or planning to engage in an alternative NHS rehabilitation programme in the next 12 weeks; 5) a member of the same household previously randomised in the present study. Intervention and comparator Intervention 1: The Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) programme: an eight week, online, home-based, supervised, group rehabilitation programme. Intervention 2: A thirty-minute, on-line, one-to-one consultation with a REGAIN practitioner (best-practice usual care). Main outcomes The primary outcome is health-related quality of life (HRQoL) – PROMIS® 29+2 Profile v2.1 (PROPr) – measured at three months post-randomisation. Secondary outcomes include dyspnoea, cognitive function, health utility, physical activity participation, post-traumatic stress disorder (PTSD) symptom severity, depressive and anxiety symptoms, work status, health and social care resource use, death - measured at three, six and 12 months post-randomisation. Randomisation Participants will be randomised to best practice usual care or the REGAIN programme on a 1:1.03 basis using a computer-generated randomisation sequence, performed by minimisation and stratified by age, level of hospital care, and case level mental health symptomatology. Once consent and baseline questionnaires have been completed by the participant online at home, randomisation will be performed automatically by a bespoke web-based system. Blinding (masking) To ensure allocation concealment from both participant and REGAIN practitioner at baseline, randomisation will be performed only after the baseline questionnaires have been completed online at home by the participant. After randomisation has been performed, participants and REGAIN practitioners cannot be blind to group allocation. Follow-up outcome assessments will be completed by participants online at home. Numbers to be randomised (sample size) A total of 535 participants will be randomised: 263 to the best-practice usual care arm, and 272 participants to the REGAIN programme arm. Trial Status Current protocol: Version 3.0 (27th October 2020) Recruitment will begin in December 2020 and is anticipated to complete by September 2021. Trial registration ISRCTN:11466448, 23rd November 2020 Full protocol The full protocol Version 3.0 (27th October 2020) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interests of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.

Introduction Chronic non-malignant pain has a major impact on the well-being, mood and productivity of those affected. Opioids are increasingly prescribed to manage this type of pain, but with a risk of other disabling symptoms, when their effectiveness has been questioned. This trial is designed to implement and evaluate a patient-centred intervention targeting withdrawal of strong opioids in people with chronic pain. Methods and analysis A pragmatic, multicentre, randomised controlled trial will assess the clinical and cost-effectiveness of a group-based multicomponent intervention combined with individualised clinical facilitator led support for the management of chronic non-malignant pain against the control intervention (self-help booklet and relaxation compact disc). An embedded process evaluation will examine fidelity of delivery and investigate experiences of the intervention. The two primary outcomes are activities of daily living (measured by Patient-Reported Outcomes Measurement Information System Pain Interference Short Form (8A)) and opioid use. The secondary outcomes are pain severity, quality of life, sleep quality, self-efficacy, adverse events and National Health Service (NHS) healthcare resource use. Participants are followed up at 4, 8 and 12 months, with a primary endpoint of 12 months. Between-group differences will indicate effectiveness; we are looking for a difference of 3.5 points on our pain interference outcome (scale 40 to 77). We will undertake an NHS perspective cost-effectiveness analysis using quality adjusted life years. Ethics and dissemination Full approval was given by Yorkshire & The Humber - South Yorkshire Research Ethics Committee on 13 September, 2016 (16/YH/0325). Appropriate local approvals were sought for each area in which recruitment was undertaken. The current protocol version is 1.6 date 19 December 2018. Publication of results in peer- reviewed journals will inform the scientific and clinical community. We will disseminate results to patient participants and study facilitators in a study newsletter as well as a lay summary of results on the study website. Trial registration number NCT49470934; Pre-results.