Amitriptyline at Low-dose and Titrated for Irritable Bowel Syndrome as Second-line Treatment in Primary Care(The ATLANTIS study): A Double-blind Placebo-controlled Trial

Conference:

SAPC ASM 2023 - Brighton

Talk Code:

2B.1

Presenter:

Hazel Everitt

Twitter:

@HazelEveritt

Co-authors:

A. C. Ford 1, A. Wright-Hughes 2, S. Alderson 3, P. Ow 2, M. Ridd 4, R. Foy 3, F. Bishop 5, M. Chaddock 6, H. Cook 7, D. Cooper 3, C. Fernandez 2, R. Thornton 8, E. Guthrie 3, S. Hartley 2, A. Herbert 4, S. Newman 8, E. Teasdale 8, A. Farrin 2, H. Everitt 8, on behalf of the ATLANTIS Trial Team 3

Author institutions:

1 Leeds Institute of Medical Research, University of Leeds, UK 2 Clinical Trials Research Unit, University of Leeds, UK 3 Leeds Institute of Health Sciences, University of Leeds, UK 4 Population Health Sciences, University of Bristol, UK 5 School of Psychology, University of Southampton, UK 6 Let’sCure IBS, UK 7 Exeter Clinical Trials Unit, University of Exeter, UK 8 Primary Care Research Centre,

Problem

Irritable bowel syndrome (IBS) is a common chronic bowel disorder causing abdominal pain, bloating and changes in bowel habit that can considerably impact patients’ quality of life and have substantial societal and health care resource costs. NICE Guidelines recommend considering low dose amitriptyline if first line treatments are ineffective, however evidence for patients in primary care is unclear and few GPs currently prescribe amitriptyline for IBS.

Approach

A NIHR HTA funded double-blind randomised placebo-controlled superiority trial of low dose amitriptyline (10-30mg self-titrated by participants) for adults with IBS in primary care.

Eligibility: Adults 18 years and over with ongoing troublesome IBS symptoms despite trying first-line IBS treatments. Normal screening bloods including FBC, CRP and TTG for coeliac screening. Exclusion criteria: meeting NICE 2-week referral criteria for suspected lower gastrointestinal cancer, coeliac disease or inflammatory bowel disease, colorectal cancer, pregnancy, breastfeeding, or current use of, allergy to, or contraindications to amitriptyline or tricyclic antidepressants.

Recruitment was via GP letter invite and opportunistic recruitment in GP surgeries in England through 3 recruitment hubs in Wessex, West of England, West Yorkshire.

Participants randomised 1:1 to amitriptyline or matched placebo for 6 months by an automated system at Leeds CTRU. Participants had the option to continue trial medication until 12 months. Participants, investigators, and study personnel were masked to treatment allocation. Study drugs were dispensed by a central pharmacy at Leeds Teaching Hospitals NHS Trust. Study drug appearance, packaging, and labelling were identical in both the active treatment and placebo arms.

Participant-completed assessments online or on paper at baseline and 3, 6, and 12 months post-randomisation. Primary outcome: Global symptoms of IBS at 6 months (using the IBS Symptom Severity Score). Secondary outcomes: relief of IBS symptoms, effect on IBS-associated somatic symptoms (Patient Health Questionnaire-12), anxiety and depression (Hospital Anxiety and Depression Scale), ability to work and participate in other activities (Work and Social Adjustment Scale), acceptability and tolerability of treatment, self-reported health care use, health-related quality of life (EQ-5D-3L), and cost-effectiveness. A nested, qualitative study (to be presented separately) explored patient and GP experiences of treatments and trial participation, including acceptability, adherence, unanticipated effects, and implications for wider use of amitriptyline for IBS in primary care.

Findings

463 patients were recruited from 55 GP surgeries between December 2019 and April 2022 with the support of Clinical Research Networks. This is the largest trial of amitriptyline for IBS worldwide.

Follow up is complete and data analysis is underway. Results will be available at the conference.

Consequences

Determining the clinical effectiveness of low-dose amitriptyline for IBS in primary care will provide robust evidence to enable patients and clinicians to make better informed treatment decisions.

Trial registration: ISRCTN48075063.

Submitted by:

Hazel Everitt

Funding acknowledgement:

NIHR HTA