Chyme Reinfusion for Type 2 Intestinal Failure

Study Overview
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Brief Summary
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This project aims to introduce and evaluate a novel assistive prosthetic system that helps prevent and treat nutrient and fluid loss from enterocutaneous fistulas. The device system functions simply to return the output from a fistula back into the distal limb of the intestine.

Detailed Description
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The development of enterocutaneous fistulas are devastating consequences of surgery or surgical diseases. They cause excessive fluid and nutrient losses from the gut resulting in severe dehydration and intestinal failure mandating invasive medical therapies to improve survival. These disorders inflict a vast burden of suffering, morbidity, and mortality on patients, while extracting enormous per-patient resources from healthcare systems. Parenteral nutrition is often required, meaning prolonged hospital stay, an attendant risk of line sepsis, venous damage and thrombosis, liver impairment, and death. There is a pressing demand for breakthrough technologies that can restore lost fluids and nutrients to the body in patients affected by enterocutaneous fistulas in order to reverse intestinal failure, eliminate the need for parenteral nutrition, prevent dehydration and renal injury, allow safe care in the community, enable chemotherapy completion, and restore quality of life.

Official Title
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Pivotal Study to Evaluate the Safety and Efficacy of the Insides™ System in the Treatment of Subjects With a Double Enterostomy and/or Enterocutaneous Fistula and Type 2 Intestinal Failure.

Conditions
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Intestinal Failure, Enterocutaneous Fistula, Ileostomy - Stoma

Intervention / Treatment
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* Device: The Insides System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 21 years Able to provide written informed consent Dependent on parenteral nutrition (PN) DES/ECF with exposed afferent and efferent limbs visible on the abdominal wall Minimum of 2 weeks post DES/ECF creation Distal limb of DES/ECF opening can be intubated by a minimum 24Fr feeding tube (dilatation of orifice strictures is allowable) Exclusion Criteria: Insufficient distal access channel (distal limb) for device insertion Bowel obstruction proximal to the DES/ECF Small bowel obstruction, anastomotic leak, or perforation distal to the DES/ECF (diagnostic procedure such as gastrografin test, fistulograms, or similar must be performed, if there is a distal anastomosis with integrity not previously evaluated, to ensure that the subject is eligible) Scheduled for DES/ECF reversal within 4 weeks of enrolment date Current infection with Clostridium difficile colitis Current infection small intestinal bacterial overgrowth (SIBO) Signs or symptoms of systemic infection Pre-existing gastrointestinal motility disorders including slow transit constipation, outlet obstruction, fecal incontinence, and gastroparesis Metabolic, neurogenic, or endocrine disorders known to cause colonic dysmotility, e.g., multiple sclerosis, Parkinson's disease, hypothyroidism Known peritoneal metastatic disease prior to DES/ECF closure (acceptable if only discovered at time of closure) Liver cirrhosis Hereditary coagulopathy, e.g., von Willebrand disease Severe chronic renal insufficiency prior to DES/ECF formation (eGFR<30mL/min/1.73m2) Active implantable medical devices such as neuromodulation and cardiac systems Metal stents implanted within 20cm of expected use of the controller Women who are pregnant or breastfeeding Subjects participating in an interventional clinical study within 30 days prior to randomization

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Global multi center prospective randomized controlled study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Reinfusion of chyme using the Insides System for subjects with Type II intestinal failure dependent on PN | Device: The Insides System<br>* Novel pump designed to return effluent from the ostomy bag to the distal gut<br>|
| No Intervention: Control<br>Standard of care therapies in accordance with ASPEN and ESPEN treatment guidelines | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - Proportion of subjects who discontinue the use of parenteral nutrition at 30 days | Between group comparison of the proportion of subjects who discontinue the use of parenteral nutrition | 30 days post randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - Between group comparison of the time to discontinuation of parenteral nutrition | Between group comparison of the time to discontinuation of parenteral nutrition measured in days | 30 days | 
| Efficacy - Between group comparison of the time to fistula closure | Between group comparison of the time to surgery for fistula closure measured in days | 90 days | 
| Safety - Between group comparison of the incidence of serious adverse events | Between group comparison of the incidence of serious adverse events such as dehydration, metabolic disarray, failure to complete prescribed chemotherapy, IV line complications, fistula complications, device related effects | 90 days | 
| Safety - Between group comparison of medication use to control fluid loss due to high output enterostomies | Between group comparison of the use of proton pump inhibitors, anti motility agents, histamine receptor antagonists, a2 receptor antagonists, and somatostatins. | 30 and 90 days | 
| Safety - Between group comparison of nutritional failure measured by the nutritional risk index (NRI) | Between group comparison of the nutritional risk index (NRI). Nutritional failure risk will be categorized as severe (NRI<83.5), moderate (NRI 83.5 - 97.5) and low (NRI>97.5). | 30 and 90 days | 
| Safety - Between group comparison of peristomal skin complications | Between group comparison of peristomal skin complications measured by the discoloration, erosion, tissue overgrowth (DET) score as mild, moderate or severe | 30 and 90 days | 
| Healthcare Utilization - Between group comparison of length of stay for index hospitalization | Between group comparison of length of stay for index hospitalization measured from the day of randomization to discharge | up to 30 days | 
| Healthcare Utilization - Between group comparison of all cause hospitalizations | Between group comparison of all cause hospitalizations measured by the total number of discreet hospitalizations >24 hours in duration | 90 days | 
| Healthcare Utilization - Between group comparison of hospitalizations due to dehydration | Between group comparison of hospital admissions >24 hours duration where the primary reason for admission is dehydration | 90 days | 
| Device performance - The overall incidence of device related adverse effects | The overall incidence of device related adverse effects reported in subjects randomized to the device. Effects may include effluent cycling time, device wear, device failure. | 90 days | 
| Quality of Life - Between group comparison of quality of life indices as measured by the EuroQol 5D | Between group comparison of quality of life as measured by the following: EuroQol 5D scale - a five question survey and health thermometer where 0= the worst health you can imagine and 100= the best health you can imagine. Stoma QoL - This questionnaire consists of 20 questions. An example of a question could be: I worry that the pouch will loosen. All the questions must be answered on a 4-point scale. The options for answering each question are: Always Sometimes Rarely Not at all | 30 and 90 days | 
| Quality of Life - Between group comparison of quality of life indices as measured by the Stoma QoL Questionnaire | Stoma QoL - This questionnaire consists of 20 questions. An example of a question could be: I worry that the pouch will loosen. All the questions must be answered on a 4-point scale. The options for answering each question are: Always Sometimes Rarely Not at all | 30 and 90 days | 
| Quality of Life - Between group comparison of quality of life indices as measured by the Beck Depression Inventory | Beck Depression Inventory - a 21 question survey where each question has 4 possible answers scored 0-3. The total score is summed to give an overall level of depression 1-10____________________These ups and downs are considered normal 11-16___________________ Mild mood disturbance 17-20___________________Borderline clinical depression 21-30___________________Moderate depression 31-40___________________Severe depression over 40__________________Extreme depression | 30 and 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TPN or PN, Chyme reinfusion, Intestinal failure, Parenteral nutrition, Enterocutaneous fistula, Effluent, Ileostomy - stoma