Chyme reinfusion using the Insides System to reduce parenteral nutrition dependence in Type 2 intestinal failure: multicentre randomised controlled trial (REINFUSE)

BackgroundPatients with type 2 intestinal failure (T2IF) due to double enterostomy or enterocutaneous fistula (DES/ECF) require parenteral nutrition (PN), carrying risks of catheter sepsis, venous thrombosis, and liver disease. Chyme reinfusion therapy (CRT) may reduce PN dependence but has not been evaluated in a randomised controlled trial (RCT). This study assessed whether device-assisted CRT using The Insides System reduces PN requirements. MethodsThis multicentre, open-label RCT enrolled PN-dependent adults with T2IF due to DES/ECF across 12 centres in the UK and USA. Patients with insufficient distal limb length, proximal bowel obstruction, active sepsis, or severe hepatorenal failure were excluded. Participants were block randomised 2:1 to device-assisted CRT plus standard care (active) or standard care (control). The primary endpoint was 50% or greater reduction in PN caloric intake at 30 days, using an intention-to-treat analysis, for a comparison between randomised 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. ResultsThe population comprised 39 (26 active, 13 control) participants. At Day 30, 8/26 (31%) active participants achieved the primary endpoint versus no controls (p=0.035). By Day 60, 10/23 (43%) active participants had completely ceased PN versus no controls (p=0.008), with median intestinal losses reduced by 1,344 mL/day at Day 30 (p=0.005) and 1,450 mL/day at Day 60 (p=0.026 between group). Device-related adverse events were predominantly mild; one death unrelated to the device occurred. ConclusionCRT with the Insides System demonstrated substantial therapeutic advantages in patients with T2IF from DES/ECF, with 31% of participants reducing PN calories by 50% at 30 days and >40% of participants achieving complete PN cessation by 60 days, and an acceptable safety profile. Trial registrationClinicalTrials.gov NCT04577456 FundingThis trial was sponsored by The Insides Company Ltd. Surgical RelevanceWhat is already known: Patients with type 2 intestinal failure due to double enterostomy or enterocutaneous fistula depend on parenteral nutrition, which carries significant risks including central venous catheter (CVC) sepsis, venous thrombosis, and intestinal failure-associated liver disease. Chyme reinfusion therapy restores distal gut function but has only been evaluated in non-randomised cohort studies. What is new: This first randomised controlled trial of device-assisted chyme reinfusion demonstrates that 43 per cent of participants can completely cease parenteral nutrition by 60 days, with a 70 per cent reduction in intestinal losses, high participant satisfaction and an acceptable risk profile. Potential impact on future practice: Early initiation of device-assisted chyme reinfusion in suitable patients with double enterostomy or enterocutaneous fistula reduces parenteral nutrition dependence, avoids associated complications and costs, and facilitates rehabilitation before reconstructive surgery.