Prospective randomised controlled trial of adults with perianal fistulising Crohn’s disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol
Danny Liew,
Ailsa Hart,
Niels Vande Casteele,
Jordi Rimola,
Jane M Andrews,
Jakob Begun,
Susan Connor,
Astrid-Jane Williams,
Yang Wu,
Wei Xuan,
Nik Sheng Ding,
Bonita Gu,
Michael De Gregorio,
Joseph Louis Pipicella,
William Connell,
Basil D’Souza,
Ali Gholamrezaei,
Graham Radford-Smith,
Tom Sutherland,
Catherine Toong,
Rodney Woods,
Watson Ng
Affiliations
Danny Liew
1 School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
Ailsa Hart
Inflammatory Bowel Diseases Unit, St Marks Hospital, Harrow, UK
Niels Vande Casteele
Department of Medicine, University of California San Diego, La Jolla, California, USA
Jordi Rimola
1 IBD Unit, Radiology Department, Hospital Clínic de Barcelona, Barcelona, Spain
Jane M Andrews
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
Jakob Begun
Department of Gastroenterology, Mater Hospital Brisbane, Brisbane, Queensland, Australia
Susan Connor
Department of Gastroenterology and Hepatology, Liverpool Hospital, Sydney, New South Wales, Australia
Astrid-Jane Williams
Department of Gastroenterology and Hepatology, Liverpool Hospital, Liverpool, New South Wales, Australia
Yang Wu
South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia
Wei Xuan
Ingham Institute of Applied Medical Research, Liverpool, New South Wales, Australia
Nik Sheng Ding
Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
Bonita Gu
South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia
Michael De Gregorio
Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
Joseph Louis Pipicella
Biostatistics Unit, The Ingham Institute for Applied Medical Research, Sydney, New South Wales, Australia
William Connell
Department of Gastroenterology and Hepatology, St Vincents Hospital Melbourne, Melbourne, Victoria, Australia
Basil D’Souza
4Department of Colorectal Surgery, St Vincent’s Hospital Melbourne, Melbourne, Australia
Ali Gholamrezaei
3 Faculty of Medicine and Health, The University of Sydney - Camperdown and Darlington Campus, Sydney, New South Wales, Australia
Graham Radford-Smith
4QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
Tom Sutherland
Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
Catherine Toong
South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia
Rodney Woods
Department of Colorectal Surgery, St Vincent’s Hospital Melbourne, Melbourne, Victoria, Australia
Watson Ng
Department of Gastroenterology and Hepatology, Liverpool Hospital, Liverpool, New South Wales, Australia
Introduction Perianal fistulising Crohn’s disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeutic drug monitoring (TDM) improves outcomes. This randomised controlled trial aimed to assess whether infliximab therapy targeting higher TLIs guided by proactive TDM improves outcomes compared with standard therapy.Methods and analysis Patients with active pfCD will be randomised 1:1 to either the proactive TDM arm or standard dosing arm and followed up for 54 weeks. Patients in the proactive TDM arm will have infliximab dosing optimised to target higher TLIs. The targets will be TLI ≥ 25 µg/mL at week 2, ≥ 20 µg/mL at week 6 and ≥ 10 µg/mL during maintenance therapy. The primary objective will be fistula healing at week 32. Secondary objectives will include fistula healing, fistula closure, radiological fistula healing, patient-reported outcomes and economic costs up to 54 weeks. Patients in the standard dosing arm will receive conventional infliximab dosing not guided by TLIs (5 mg/kg at weeks 0, 2 and 6, and 5 mg/kg 8 weekly thereafter). Patients aged 18–80 years with pfCD with single or multiple externally draining complex perianal fistulas who are relatively naïve to infliximab treatment will be included. Patients with diverting ileostomies or colostomies and pregnant or breast feeding will be excluded. Fifty-eight patients per arm will be required to detect a 25% difference in the primary outcome measure, with 138 patients needed to account for an estimated 6.1% primary non-response rate and 10% dropout rate.Ethics and dissemination Results will be presented in peer-reviewed journals and international conferences. Ethics approval has been granted by the South Western Sydney Local Health District Human Research Ethics Committee in Australia.Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12621000023853); Pre-results.
