Chyme reinfusion using The Insides® System to reduce parenteral nutrition dependence in type 2 intestinal failure: multicentre randomized clinical trial (REINFUSE).
14 affiliations
- 1Department of Colorectal Surgery, Royal Brisbane and Women's Hospital, Brisbane, Australia.
- 2Gastroenterology, Northern Care Alliance NHS Foundation Trust, Manchester, UK.
- 3Colorectal Surgery, Nottingham University Hospitals NHS Trust, Nottingham, UK.
- 4Colorectal Surgery, London North West University Healthcare NHS Trust, London, UK.
- 5Colorectal Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
- 6Colorectal Surgery, Newcastle Hospitals NHS Foundation Trust, Newcastle, UK.
- 7Gastrolenterology, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK.
- 8Department of Surgery, University of Nebraska Medical Center, Omaha, USA.
- 9Trauma Surgery, University of Miami Health System, Miami, USA.
- 10Gastroenterology and Hepatology, University of Illinois Chicago, Chicago, USA.
- 11Department of Surgery, University of Florida, Gainesville, USA.
- 12Gastroenterology and Hepatology, Henry Ford Health, Detroit, USA.
- 13Department of Medicine, University of Otago, Christchurch, New Zealand.
- 14Abdominal Medicine & Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Abstract
Background
Patients with type 2 intestinal failure due to double enterostomy or enterocutaneous fistula requiring parenteral nutrition (PN), are at higher risks of catheter sepsis, venous thrombosis, and liver disease. Chyme reinfusion therapy (CRT) may reduce PN dependence but has not been evaluated in a randomized clinical trial. This study assessed whether device-assisted CRT using The Insides® System reduces PN requirements.Methods
This multicentre, open-label randomized clinical trial enrolled PN-dependent adults with type 2 intestinal failure due to double enterostomy or enterocutaneous fistula across 12 centres in the UK and USA between 2022 and 2025. Patients with insufficient distal limb length, proximal bowel obstruction, active sepsis, or severe hepatorenal failure were excluded. Participants were block randomized 2 : 1 to device-assisted CRT plus standard care (active) or standard care (control). The primary endpoint was ≥ 50% reduction in PN caloric intake at 30 days, using an intention-to-treat analysis, for a comparison between randomized groups using a two-tailed P value of 0.025 to allow for a single interim analysis. Secondary outcomes were rate of PN cessation at 30 and 60 days, quality of life, and adverse events.Results
Out of 44 patients assessed for eligibility, 39 patients were randomized (26 CRT plus standard care-active, 13 standard care control). At day 30, 8 of 26 active participants (31%) achieved the primary endpoint versus no controls (P = 0.035). By day 60, 10 of 23 active participants (42%) had completely ceased PN versus no controls (P = 0.011), with median intestinal losses reduced by 1344 ml/day at day 30 (P = 0.005) and 1450 ml/day at day 60 (P = 0.026 between group). There were 11 device-related adverse events, one severe and all resolved. There was one death unrelated to the device.Conclusion
Although the study's primary endpoint did not reach statistical significance, at 30 days, 31% of participants undergoing CRT had reduced PN calories by 50%, and at 60 days > 40% of CRT patients had completely ceased PN, with an acceptable safety profile.Registration number
NCT04577456 (http://www.clinicaltrials.gov).
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BibTeX
@article{milne2026chyme,
title = {{Chyme reinfusion using The Insides® System to reduce parenteral nutrition dependence in type 2 intestinal failure: multicentre randomized clinical trial (REINFUSE).}},
author = {Tony G E Milne and Simon Lal and Arun Abraham and Kirstine Farrer and Jonathan Evans and Kathryn Thomas and Carolynne Vaizey and Simon Gabe and David Layfield and Neena Randhawa and John Rogers and David F Mercer and Liran Barda and Robert E Carroll and Martin D Rosenthal and Syed-Mohammed Jafri and Chris Frampton and Dermot Burke},
journal = {BJS open},
year = {2026},
month = sep,
doi = {10.1093/bjsopen/zrag158},
url = {https://europepmc.org/article/MED/42911833},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Chyme reinfusion using The Insides® System to reduce parenteral nutrition dependence in type 2 intestinal failure: multicentre randomized clinical trial (REINFUSE).
AU - Tony G E Milne
AU - Simon Lal
AU - Arun Abraham
AU - Kirstine Farrer
AU - Jonathan Evans
AU - Kathryn Thomas
AU - Carolynne Vaizey
AU - Simon Gabe
AU - David Layfield
AU - Neena Randhawa
AU - John Rogers
AU - David F Mercer
AU - Liran Barda
AU - Robert E Carroll
AU - Martin D Rosenthal
AU - Syed-Mohammed Jafri
AU - Chris Frampton
AU - Dermot Burke
PY - 2026
DA - 2026/09/01
JO - BJS open
DO - 10.1093/bjsopen/zrag158
UR - https://europepmc.org/article/MED/42911833
AB - Background Patients with type 2 intestinal failure due to double enterostomy or enterocutaneous fistula requiring parenteral nutrition (PN), are at higher risks of catheter sepsis, venous thrombosis, and liver disease. Chyme reinfusion therapy (CRT) may reduce PN dependence but has not been evaluated in a randomized clinical trial. This study assessed whether device-assisted CRT using The Insides® System reduces PN requirements.Methods This multicentre, open-label randomized clinical trial enrolled PN-dependent adults with type 2 intestinal failure due to double enterostomy or enterocutaneous fistula across 12 centres in the UK and USA between 2022 and 2025. Patients with insufficient distal limb length, proximal bowel obstruction, active sepsis, or severe hepatorenal failure were excluded. Participants were block randomized 2 : 1 to device-assisted CRT plus standard care (active) or standard care (control). The primary endpoint was ≥ 50% reduction in PN caloric intake at 30 days, using an intention-to-treat analysis, for a comparison between randomized groups using a two-tailed P value of 0.025 to allow for a single interim analysis. Secondary outcomes were rate of PN cessation at 30 and 60 days, quality of life, and adverse events.Results Out of 44 patients assessed for eligibility, 39 patients were randomized (26 CRT plus standard care-active, 13 standard care control). At day 30, 8 of 26 active participants (31%) achieved the primary endpoint versus no controls (P = 0.035). By day 60, 10 of 23 active participants (42%) had completely ceased PN versus no controls (P = 0.011), with median intestinal losses reduced by 1344 ml/day at day 30 (P = 0.005) and 1450 ml/day at day 60 (P = 0.026 between group). There were 11 device-related adverse events, one severe and all resolved. There was one death unrelated to the device.Conclusion Although the study's primary endpoint did not reach statistical significance, at 30 days, 31% of participants undergoing CRT had reduced PN calories by 50%, and at 60 days > 40% of CRT patients had completely ceased PN, with an acceptable safety profile.Registration number NCT04577456 (http://www.clinicaltrials.gov).
SN - 2474-9842
ER -