Adhesions, Ileus
Conditions
Keywords
post-operative, abdominal
Brief summary
The purpose of this study is to assess the safety, tolerability, and preliminary efficacy of LB1148 in subjects undergoing elective bowel resection. During abdominal surgery, surgeons handle, manipulate, and often make incisions in the bowel. These actions can create bruising, lesions, and microscopic damage to the bowel, which may allow digestive enzymes to cross the intestinal mucosal barrier potentially resulting in injury both locally and remotely. Leaking digestive enzymes may delay return of normal gastrointestinal (GI) function, lead to a lack of motility in the intestine (ileus), and promote the formation of intestinal scar tissue (adhesions).
Detailed description
The intestinal mucosal barrier plays a key role in both acute critical care medical conditions as well as burdensome chronic diseases. Healthy maintenance of the intestinal mucosal barrier requires oxygenation and blood flow and avoidance of mechanical or physical injury. Potent digestive enzymes are maintained within the intestine as long as normal blood flow continues and no damage or disturbances to the wall occur. Breakdown of the intestinal mucosal barrier can be produced by wide variety of events. These include prolonged low blood pressure (e.g. during shock), disruption of blood flow (e.g. during ischemia), and physical and mechanical perturbations (e.g. during trauma or abdominal surgery). One of the key advances toward the use of LB1148 to reduce postoperative complications was the learning that with more subtle perturbations of the mucosal barriers, such as during abdominal surgery, intraluminal pancreatic digestive enzymes played a role in GI dysfunction. Perioperative oral administration of LB1148 in preclinical models was sufficient to reduce the delayed return of GI function. Furthermore, the reduction in pancreatic digestive enzyme-induced tissue damage resulted in a profound reduction in postoperative adhesion formation. Together, these preclinical studies provide evidence that blocking pancreatic digestive enzymes with LB1148 in the intestine reduces local tissue damage, preserves GI function, and reduces adhesion formation.
Interventions
DRUGTranexamic Acid
A total of 700 mL of study drug should be completely consumed orally 2-12 hours prior to surgery as a split dose; 350 mL 6-12 hours prior to surgery and the remaining 350 mL 2-6 hours prior to surgery.
Sponsors
Ronald Hurst, MD, FACS
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
This is an investigator-initiated, open label, Phase 1 study to evaluate LB1148 for safety, tolerability, and preliminary efficacy in subjects undergoing elective bowel resection. All subjects will receive LB1148 prior to surgery.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Subjects will be eligible for participation in the study only if they meet ALL of the following inclusion criteria: 1. Scheduled to undergo an elective (non-emergent) bowel resection. This includes any subject in which a resection of the small intestine, colon, or rectum is performed for any elected indication. 2. The subject has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent.
Exclusion criteria
* Subjects will not be eligible for participation in the study if they meet ANY of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The number of participants who experience treatment-emergent adverse events (TEAEs) | From first study drug dosing through Day 30 | The number of participants who experience treatment-emergent adverse events (TEAEs) with Investigator-specified relationship to LB1148 and assessment of severity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average length of time an NG tube was in place, if required | During hospitalization (up to 14 days postoperatively), in hours | Time NG tube was in place, if needed |
| Number of participants who experience post surgical vomiting | During hospitalization (from surgical closure to up to 14 days postoperatively), yes or no | Presence of postsurgical vomiting |
| Average number of vomiting episodes, when present | During hospitalization (from surgical closure to up to 14 days postoperatively), number of total episodes | Number of vomiting episode(s) |
| Average time to first flatus following surgery | During hospitalization (from surgical closure to up to 14 days postoperatively), in hours | Time to first flatus |
| Number of participants who require a nasogastric (NG) tube placement | During hospitalization (up to 14 days postoperatively), yes or no | Necessity for nasogastric (NG) tube placement |
| Average time to tolerate a liquid diet following surgery | During hospitalization (from surgical closure to up to 14 days postoperatively), in hours | Time to toleration of a liquid diet |
| Average time to tolerate a solid diet after surgery | During hospitalization (from surgical closure to up to 14 days postoperatively), in hours | Time to toleration of a solid diet |
| Average time to hospital discharge order | During hospitalization (from admission to up to 14 days postoperatively), in hours | Time to hospital discharge order written |
| Average time to first bowel movement following surgery | During hospitalization (from surgical closure to up to 14 days postoperatively), in hours | Time to first bowel movement |
Countries
United States
Outcome results
None listed