Teduglutide for Enterocutaneous Fistula (ECF)

• Sponsor: Daniel Dante Yeh (Other)
• Overall Status: Completed
• CT.gov ID: NCT02889393
• Collaborator: Takeda (Industry)
• Enrollment: 6
• Location: 1
• Arms: 2
• Actual Duration (Months): 29.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether Teduglutide is safe and feasible to be given for the treatment of enterocutaneous fistula (ECF). The hypothesis is that the drug will be well tolerated and will improve the volume of daily ECF output as well as improve the functional quality of life.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Fistula	Drug: Teduglutide; Other: Standard of Care	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Teduglutide for Treatment of Enterocutaneous Fistula (ECF) - a Pilot Study to Demonstrate Safety and Feasibility
• Actual Study Start Date: Jan 31, 2019
• Actual Primary Completion Date: Jul 15, 2020
• Actual Study Completion Date: Jul 15, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Standard of Care followed by Teduglutide Participants in this group will receive standard of care treatment for the first 8 weeks followed by daily Teduglutide for the next 8 weeks. Subjects with a favorable response will be offered an open label extension during which they will continue to receive teduglutide for up to another 12 months or permanent fistula closure.	Drug: Teduglutide; Daily 0.05 mg/kg Teduglutide administered subcutaneously.; Other Names: Gattex ; Other: Standard of Care; The standard of care treatment of ECF which includes meticulous wound care, optimizations of nutrition, use of acid-suppression medications and anti-motility agents as per treating physician discretion.
Experimental: Teduglutide followed by Standard of Care Participants in this group will receive daily Teduglutide treatment for the first 8 weeks followed by standard of care for the next 8 weeks. Subjects with a favorable response will be offered an open label extension during which they will continue to receive teduglutide for up to another 12 months or permanent fistula closure	Drug: Teduglutide; Daily 0.05 mg/kg Teduglutide administered subcutaneously.; Other Names: Gattex ; Other: Standard of Care; The standard of care treatment of ECF which includes meticulous wound care, optimizations of nutrition, use of acid-suppression medications and anti-motility agents as per treating physician discretion.

Outcome Measures

Primary Outcome Measures

1. Change in Average 3-day Fistula Percent Volume [Baseline, Up to 8 weeks]

   Percent fistula volume will be reported from the participant

Secondary Outcome Measures

1. Number of Participants With Ceased Fistula Output [Up to 16 weeks]

   As evaluated by treating physician of having at least 1 ceased fistula output

2. Quality of Life as Measured by ASCQ-Me® v2.0 Social Functioning - Short Form [Up to 16 weeks]

   Adult Sickle Cell Quality of Life Measurement (ASCQ-Me) Version 2.0 Social Functioning - Short Form questionnaire has a total score ranging from 5-25 with the higher score indicating a healthier status.

3. Quality of Life as Measured by the ASCQ-Me® v2.0 Sleep Impact - Short Form [Up to 16 weeks]

   Adult Sickle Cell Quality of Life Measurement (ASCQ-Me) Version 2.0 Sleep Impact - Short Form questionnaire has a total score ranging from 5-25 with the higher score indicating a healthier status

4. Quality of Life as Measured by the PROMIS Scale v1.2 - Global Health [Up to 16 weeks]

   Patient Reported Outcome Measures Information Systems Global Health has a total score ranging from 10-50 with the higher score indicating a healthier status

5. Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Belly Pain 5a [Up to 16 weeks]

   Patient Reported Outcome Measures Information Systems (PROMIS-GI) Gastrointestinal Belly Pain 5a questionnaire has a total score ranging from 1-25 with the lower score indicating a healthier status

6. Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Diarrhea 6a [Up to 16 weeks]

   Patient Reported Outcome Measures Information Systems (PROMIS-GI) Gastrointestinal Diarrhea 6a questionnaire has a total score ranging from 1-30 with the lower score indicating a healthier status

7. Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Nausea and Vomiting 4a [Up to 16 weeks]

   Patient Reported Outcome Measures Information Systems (PROMIS-GI) Gastrointestinal Nausea and Vomiting 4a questionnaire has a total score ranging from 1-20 with the lower score indicating a healthier status

8. Quality of Life as Measured by the PROMIS Scale v2.0 - Ability to Participate in Social Roles and Activities - Short Form 8a [Up to 16 weeks]

   Patient Reported Outcome Measures Information Systems (PROMIS) Ability to Participate in Social Roles and Activities - Short Form 8a questionnaire has a total score ranging from 8-40 with the lower score indicating a healthier status

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age >18

• Enterocutaneous fistula (ECF) that could be secondary to volvulus, injury, prior trauma or surgery, or vascular ischemia

Exclusion Criteria:

• Perianal fistula

• Clinical suspicion of inflammatory bowel disease

• History of radiation enteritis or sprue (as defined by history)

• Active (<1 year) alcohol or drug abuse

• Significant hepatic, or cardiac diseases as defined as:

• Hepatic: aspartate aminotransferase (AST) > 2 times upper limit of normal (10-40 U/L)

• Cardiac: unstable angina or evidence of active myocardial ischemia (elevated troponin level drawn by clinical suspicion)

• Severe renal dysfunction: serum creatinine > 2 times upper limit of normal (0.6-1.5 mg/dL)

• Received glutamine less than 4 weeks prior to screening

• Receiving growth factors (erythropoietin, granulocyte colony-stimulating factor, granulo-cyte-macrophage colony stimulating factor, and human growth hormone)

• Pregnancy or lactation (women of childbearing age will be excluded if they do not agree to either complete sexual abstinence during the study or if they refuse to use at least two forms of highly effective contraception such as oral contraception, injectable or implantable contraception, vaginal rings, or intrauterine devices (IUD))

• Active malignancy or suspicion for gastrointestinal malignancy on CT scan

• Not capable of understanding or not willing to adhere to the study visit schedule and drug administration requirements

• Family history of intestinal malignancy (gastric, small intestine, colon)

• Personal or family history of hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, first degree relative with colon cancer

• Positive hemoccult (per rectum)

• Abnormal baseline electrocardiogram (ECF) suggestive of congestive heart failure or underlying cardiac disease

• Taking oral benzodiazepines, barbiturates, or phenothiazines

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami	Miami	Florida	United States	33136

Sponsors and Collaborators

• Daniel Dante Yeh
• Takeda

Investigators

• Principal Investigator: Daniel D Yeh, MD, University of Miami

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 16, 2021

More Information

Publications

• Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B, O'Keefe SJ. Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut. 2011 Jul;60(7):902-14. doi: 10.1136/gut.2010.218271. Epub 2011 Feb 11.
• Jeppesen PB, Lund P, Gottschalck IB, Nielsen HB, Holst JJ, Mortensen J, Poulsen SS, Quistorff B, Mortensen PB. Short bowel patients treated for two years with glucagon-like Peptide 2: effects on intestinal morphology and absorption, renal function, bone and body composition, and muscle function. Gastroenterol Res Pract. 2009;2009:616054. doi: 10.1155/2009/616054. Epub 2009 Aug 20.

• Responsible Party: Daniel Dante Yeh, Associate Professor of Surgery, University of Miami
• ClinicalTrials.gov Identifier: NCT02889393
• Other Study ID Numbers: 20170189
• First Posted: Sep 5, 2016
• Last Update Posted: Oct 6, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Intestinal Fistula; Fistula; Teduglutide

Study Results

Participant Flow

Arm/Group Title	Standard of Care Followed by Teduglutide	Teduglutide Followed by Standard of Care
Arm/Group Description	Participants in this group will receive standard of care treatment for the first 8 weeks followed by daily Teduglutide for the next 8 weeks. Subjects with a favorable response will be offered an open label extension during which they will continue to receive teduglutide for up to another 12 months or permanent fistula closure. Teduglutide: Daily 0.05 mg/kg Teduglutide administered subcutaneously. Standard of Care: The standard of care treatment of ECF which includes meticulous wound care, optimizations of nutrition, use of acid-suppression medications and anti-motility agents as per treating physician discretion.	Participants in this group will receive daily Teduglutide treatment for the first 8 weeks followed by standard of care for the next 8 weeks. Subjects with a favorable response will be offered an open label extension during which they will continue to receive teduglutide for up to another 12 months or permanent fistula closure Teduglutide: Daily 0.05 mg/kg Teduglutide administered subcutaneously. Standard of Care: The standard of care treatment of ECF which includes meticulous wound care, optimizations of nutrition, use of acid-suppression medications and anti-motility agents as per treating physician discretion.
Period Title: Overall Study
STARTED	3	3
COMPLETED	3	3
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Standard of Care Followed by Teduglutide	Teduglutide Followed by Standard of Care	Total
Arm/Group Description	Participants in this group will receive standard of care treatment for the first 8 weeks followed by daily Teduglutide for the next 8 weeks. Subjects with a favorable response will be offered an open label extension during which they will continue to receive teduglutide for up to another 12 months or permanent fistula closure. Teduglutide: Daily 0.05 mg/kg Teduglutide administered subcutaneously. Standard of Care: The standard of care treatment of ECF which includes meticulous wound care, optimizations of nutrition, use of acid-suppression medications and anti-motility agents as per treating physician discretion.	Participants in this group will receive daily Teduglutide treatment for the first 8 weeks followed by standard of care for the next 8 weeks. Subjects with a favorable response will be offered an open label extension during which they will continue to receive teduglutide for up to another 12 months or permanent fistula closure Teduglutide: Daily 0.05 mg/kg Teduglutide administered subcutaneously. Standard of Care: The standard of care treatment of ECF which includes meticulous wound care, optimizations of nutrition, use of acid-suppression medications and anti-motility agents as per treating physician discretion.	Total of all reporting groups
Overall Participants	3	3	6
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	2 66.7%	5 83.3%
>=65 years	0 0%	1 33.3%	1 16.7%
Sex: Female, Male (Count of Participants)
Female	0 0%	2 66.7%	2 33.3%
Male	3 100%	1 33.3%	4 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 33.3%	1 33.3%	2 33.3%
Not Hispanic or Latino	2 66.7%	2 66.7%	4 66.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 33.3%	0 0%	1 16.7%
White	2 66.7%	3 100%	5 83.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change in Average 3-day Fistula Percent Volume
Description	Percent fistula volume will be reported from the participant
Time Frame	Baseline, Up to 8 weeks

Outcome Measure Data

Analysis Population Description

This is a cross-over study. Each participant received both teduglutide intervention and the standard of care intervention for 8 weeks each.

Arm/Group Title	Teduglutide Intervention	Standard of Care Intervention
Arm/Group Description	Participants that received Teduglutide for 8 weeks	Participants that received Standard of Care for 8 weeks
Measure Participants	6	6
Mean (Standard Deviation) [Percent change in fistula volume]	76.33 (355.36)	441.67 (824.87)

2. Secondary Outcome

Title	Number of Participants With Ceased Fistula Output
Description	As evaluated by treating physician of having at least 1 ceased fistula output
Time Frame	Up to 16 weeks

Outcome Measure Data

Analysis Population Description

Ceased fistula output was reported for all participants at the end of treatment after receiving both interventions.

Arm/Group Title	All Participants
Arm/Group Description	Participants that received both standard of care and teduglutide interventions after a combined 16 weeks
Measure Participants	6
Count of Participants [Participants]	3 100%

3. Secondary Outcome

Title	Quality of Life as Measured by ASCQ-Me® v2.0 Social Functioning - Short Form
Description	Adult Sickle Cell Quality of Life Measurement (ASCQ-Me) Version 2.0 Social Functioning - Short Form questionnaire has a total score ranging from 5-25 with the higher score indicating a healthier status.
Time Frame	Up to 16 weeks

Outcome Measure Data

Analysis Population Description

This is a cross-over study. Each participant received both teduglutide intervention and the standard of care intervention for 8 weeks each.

Arm/Group Title	Teduglutide Intervention	Standard of Care Intervention
Arm/Group Description	Participants that received Teduglutide for 8 weeks	Participants that received Standard of Care for 8 weeks
Measure Participants	6	6
Median (Standard Deviation) [score on a scale]	20.5 (5.2)	20 (7.7)

4. Secondary Outcome

Title	Quality of Life as Measured by the ASCQ-Me® v2.0 Sleep Impact - Short Form
Description	Adult Sickle Cell Quality of Life Measurement (ASCQ-Me) Version 2.0 Sleep Impact - Short Form questionnaire has a total score ranging from 5-25 with the higher score indicating a healthier status
Time Frame	Up to 16 weeks

Outcome Measure Data

Analysis Population Description

This is a cross-over study. Each participant received both teduglutide intervention and the standard of care intervention for 8 weeks each.

Arm/Group Title	Teduglutide Intervention	Standard of Care Intervention
Arm/Group Description	Participants that received Teduglutide for 8 weeks	Participants that received Standard of Care for 8 weeks
Measure Participants	6	6
Median (Standard Deviation) [score on a scale]	19.5 (1.3)	19.5 (4.1)

5. Secondary Outcome

Title	Quality of Life as Measured by the PROMIS Scale v1.2 - Global Health
Description	Patient Reported Outcome Measures Information Systems Global Health has a total score ranging from 10-50 with the higher score indicating a healthier status
Time Frame	Up to 16 weeks

Outcome Measure Data

Analysis Population Description

This is a cross-over study. Each participant received both teduglutide intervention and the standard of care intervention for 8 weeks each. 1 participant in the teduglutide arm did not complete the global health questionnaire.

Arm/Group Title	Teduglutide Intervention	Standard of Care Intervention
Arm/Group Description	Participants that received Teduglutide for 8 weeks	Participants that received Standard of Care for 8 weeks
Measure Participants	5	6
Median (Standard Deviation) [score on a scale]	30 (6.3)	35 (10.2)

6. Secondary Outcome

Title	Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Belly Pain 5a
Description	Patient Reported Outcome Measures Information Systems (PROMIS-GI) Gastrointestinal Belly Pain 5a questionnaire has a total score ranging from 1-25 with the lower score indicating a healthier status
Time Frame	Up to 16 weeks

Outcome Measure Data

Analysis Population Description

This is a cross-over study. Each participant received both teduglutide intervention and the standard of care intervention for 8 weeks each.

Arm/Group Title	Teduglutide Intervention	Standard of Care Intervention
Arm/Group Description	Participants that received Teduglutide for 8 weeks	Participants that received Standard of Care for 8 weeks
Measure Participants	6	6
Median (Standard Deviation) [score on a scale]	6.0 (8.2)	7.5 (6.9)

7. Secondary Outcome

Title	Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Diarrhea 6a
Description	Patient Reported Outcome Measures Information Systems (PROMIS-GI) Gastrointestinal Diarrhea 6a questionnaire has a total score ranging from 1-30 with the lower score indicating a healthier status
Time Frame	Up to 16 weeks

Outcome Measure Data

Analysis Population Description

This is a cross-over study. Each participant received both teduglutide intervention and the standard of care intervention for 8 weeks each.

Arm/Group Title	Teduglutide Intervention	Standard of Care Intervention
Arm/Group Description	Participants that received Teduglutide for 8 weeks	Participants that received Standard of Care for 8 weeks
Measure Participants	6	6
Median (Standard Deviation) [score on a scale]	8.0 (4.4)	6.0 (4.0)

8. Secondary Outcome

Title	Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Nausea and Vomiting 4a
Description	Patient Reported Outcome Measures Information Systems (PROMIS-GI) Gastrointestinal Nausea and Vomiting 4a questionnaire has a total score ranging from 1-20 with the lower score indicating a healthier status
Time Frame	Up to 16 weeks

Outcome Measure Data

Analysis Population Description

This is a cross-over study. Each participant received both teduglutide intervention and the standard of care intervention for 8 weeks each.

Arm/Group Title	Teduglutide Intervention	Standard of Care Intervention
Arm/Group Description	Participants that received Teduglutide for 8 weeks	Participants that received Standard of Care for 8 weeks
Measure Participants	6	6
Median (Standard Deviation) [score on a scale]	3.0 (2.8)	3.5 (3.3)

9. Secondary Outcome

Title	Quality of Life as Measured by the PROMIS Scale v2.0 - Ability to Participate in Social Roles and Activities - Short Form 8a
Description	Patient Reported Outcome Measures Information Systems (PROMIS) Ability to Participate in Social Roles and Activities - Short Form 8a questionnaire has a total score ranging from 8-40 with the lower score indicating a healthier status
Time Frame	Up to 16 weeks

Outcome Measure Data

Analysis Population Description

This is a cross-over study. Each participant received both teduglutide intervention and the standard of care intervention for 8 weeks each.

Arm/Group Title	Teduglutide Intervention	Standard of Care Intervention
Arm/Group Description	Participants that received Teduglutide for 8 weeks	Participants that received Standard of Care for 8 weeks
Measure Participants	6	6
Median (Standard Deviation) [score on a scale]	32.0 (7.8)	34.0 (13.0)

Adverse Events

Time Frame	Up to 19 months
Arm/Group Title	On Teduglutide		On Standard of Care
Arm/Group Description	The study is a crossover design. All participants received 8 weeks of daily Teduglutide. Teduglutide: Daily 0.05 mg/kg Teduglutide administered subcutaneously.		The study is a crossover design. All participants received 8 weeks of daily Standard of Care Therapy. Standard of Care: The standard of care treatment of ECF which includes meticulous wound care, optimizations of nutrition, use of acid-suppression medications and anti-motility agents as per treating physician discretion.
All Cause Mortality
	On Teduglutide		On Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Serious Adverse Events
	On Teduglutide		On Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	On Teduglutide		On Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		2/6 (33.3%)
Gastrointestinal disorders
Nausea	0/6 (0%)	0	1/6 (16.7%)	1
Vomiting	0/6 (0%)	0	1/6 (16.7%)	1
General disorders
Headache	1/6 (16.7%)	1	0/6 (0%)	0
Infections and infestations
Upper Respiratory Infection	0/6 (0%)	0	1/6 (16.7%)	1
Musculoskeletal and connective tissue disorders
Leg Cramps	0/6 (0%)	0	1/6 (16.7%)	1
Right Sided Chest Pain	0/6 (0%)	0	1/6 (16.7%)	1
Renal and urinary disorders
Increased Creatinine	1/6 (16.7%)	1	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Stoma hypertrophy	1/6 (16.7%)	1	0/6 (0%)	0
Pain at fistula site	0/6 (0%)	0	1/6 (16.7%)	1
Lip Swelling	1/6 (16.7%)	1	0/6 (0%)	0
Small Bleeding from Fistula	1/6 (16.7%)	1	0/6 (0%)	0
Edema around ostomy site	1/6 (16.7%)	1	0/6 (0%)	0
Cellulitis	0/6 (0%)	0	1/6 (16.7%)	1
Surgical and medical procedures
IV Infiltration	1/6 (16.7%)	1	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.