Postoperative Fistula
Conditions
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.
Interventions
DRUGTeduglutide
Daily 0.05 mg/kg Teduglutide administered subcutaneously.
OTHERStandard 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.
Sponsors
Takeda
Daniel Dante Yeh
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Average 3-day Fistula Percent Volume | Baseline, Up to 8 weeks | Percent fistula volume will be reported from the participant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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 |
| Number of Participants With Ceased Fistula Output | Up to 16 weeks | As evaluated by treating physician of having at least 1 ceased fistula output |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 3 |
| 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
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. | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | Standard of Care Followed by Teduglutide | Teduglutide Followed by Standard of Care | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 6 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Change in Average 3-day Fistula Percent Volume
Percent fistula volume will be reported from the participant
Time frame: Baseline, Up to 8 weeks
Population: This is a cross-over study. Each participant received both teduglutide intervention and the standard of care intervention for 8 weeks each.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide Intervention | Change in Average 3-day Fistula Percent Volume | 76.33 Percent change in fistula volume | Standard Deviation 355.36 |
| Standard of Care Intervention | Change in Average 3-day Fistula Percent Volume | 441.67 Percent change in fistula volume | Standard Deviation 824.87 |
Secondary
Number of Participants With Ceased Fistula Output
As evaluated by treating physician of having at least 1 ceased fistula output
Time frame: Up to 16 weeks
Population: Ceased fistula output was reported for all participants at the end of treatment after receiving both interventions.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teduglutide Intervention | Number of Participants With Ceased Fistula Output | 3 Participants |
Secondary
Quality of Life as Measured by ASCQ-Me® v2.0 Social Functioning - Short Form
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
Population: This is a cross-over study. Each participant received both teduglutide intervention and the standard of care intervention for 8 weeks each.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Teduglutide Intervention | Quality of Life as Measured by ASCQ-Me® v2.0 Social Functioning - Short Form | 20.5 score on a scale | Standard Deviation 5.2 |
| Standard of Care Intervention | Quality of Life as Measured by ASCQ-Me® v2.0 Social Functioning - Short Form | 20 score on a scale | Standard Deviation 7.7 |
Secondary
Quality of Life as Measured by the ASCQ-Me® v2.0 Sleep Impact - Short Form
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
Population: This is a cross-over study. Each participant received both teduglutide intervention and the standard of care intervention for 8 weeks each.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Teduglutide Intervention | Quality of Life as Measured by the ASCQ-Me® v2.0 Sleep Impact - Short Form | 19.5 score on a scale | Standard Deviation 1.3 |
| Standard of Care Intervention | Quality of Life as Measured by the ASCQ-Me® v2.0 Sleep Impact - Short Form | 19.5 score on a scale | Standard Deviation 4.1 |
Secondary
Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Belly Pain 5a
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
Population: This is a cross-over study. Each participant received both teduglutide intervention and the standard of care intervention for 8 weeks each.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Teduglutide Intervention | Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Belly Pain 5a | 6.0 score on a scale | Standard Deviation 8.2 |
| Standard of Care Intervention | Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Belly Pain 5a | 7.5 score on a scale | Standard Deviation 6.9 |
Secondary
Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Diarrhea 6a
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
Population: This is a cross-over study. Each participant received both teduglutide intervention and the standard of care intervention for 8 weeks each.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Teduglutide Intervention | Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Diarrhea 6a | 8.0 score on a scale | Standard Deviation 4.4 |
| Standard of Care Intervention | Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Diarrhea 6a | 6.0 score on a scale | Standard Deviation 4 |
Secondary
Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Nausea and Vomiting 4a
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
Population: This is a cross-over study. Each participant received both teduglutide intervention and the standard of care intervention for 8 weeks each.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Teduglutide Intervention | Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Nausea and Vomiting 4a | 3.0 score on a scale | Standard Deviation 2.8 |
| Standard of Care Intervention | Quality of Life as Measured by the PROMIS Scale v1.0 - Gastrointestinal Nausea and Vomiting 4a | 3.5 score on a scale | Standard Deviation 3.3 |
Secondary
Quality of Life as Measured by the PROMIS Scale v1.2 - Global Health
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
Population: 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 | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Teduglutide Intervention | Quality of Life as Measured by the PROMIS Scale v1.2 - Global Health | 30 score on a scale | Standard Deviation 6.3 |
| Standard of Care Intervention | Quality of Life as Measured by the PROMIS Scale v1.2 - Global Health | 35 score on a scale | Standard Deviation 10.2 |
Secondary
Quality of Life as Measured by the PROMIS Scale v2.0 - Ability to Participate in Social Roles and Activities - Short Form 8a
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
Population: This is a cross-over study. Each participant received both teduglutide intervention and the standard of care intervention for 8 weeks each.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Teduglutide Intervention | Quality of Life as Measured by the PROMIS Scale v2.0 - Ability to Participate in Social Roles and Activities - Short Form 8a | 32.0 score on a scale | Standard Deviation 7.8 |
| Standard of Care Intervention | Quality of Life as Measured by the PROMIS Scale v2.0 - Ability to Participate in Social Roles and Activities - Short Form 8a | 34.0 score on a scale | Standard Deviation 13 |