Crohn Disease, Rectal Fistula
Conditions
Brief summary
This study is to assess whether utilizing endoscopic ultrasound(EUS) to guide treatment can improve durable fistula healing in patients with Crohn's perianal fistulas and to get preliminary information regarding the effectiveness of Adalimumab for Crohn's perianal fistulas.
Detailed description
Prospective randomized trial to assess the effectiveness of rectal EUS to guide perianal fistula treatment. Our hypothesis is that using imaging, in this case endoscopic ultrasound (EUS), to initially evaluate and then guide therapy with an anti-TNF agent (adalimumab) for fistulizing disease will lead to better short- and long-term outcomes.
Interventions
PROCEDUREEUA with seton placement if necessary
Patients randomized to the combination therapy group, the surgeon will have access to EUS findings.
DRUGadalimumab
Patients began therapy with adalimumab using clinic standards for dosing.
PROCEDUREEUS
Patients in combination therapy group had an EUS done every 12 weeks to help guide therapy.
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Caregiver)
Masking description
Surgeon did not have access to EUS data for the control group prior to exam under anesthesia (EUA) and surgical intervention.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A patient may be considered for study participation if all of the following apply: * Male and Female aged 18 years or older; and * A confirmed diagnosis of Crohn's disease and one or more identifiable perianal fistulas.
Exclusion criteria
A patient will be excluded from the study if one or more of the following apply: * Females who are pregnant or breast feeding; * Infliximab received within 6 weeks prior to study entry; * Patients who cannot take, or refuse to take concomitant immunosuppressive therapy with either azathioprine, 6-mercaptopurine, or methotrexate; Unless patient has been intolerant of these therapies in the past or is contraindicated as determined by the investigator; * Patients who cannot take, or refuse to take concomitant antibiotic therapy; * Patients with severe anal stenosis or tenderness which would preclude colonoscopy and / or rectal EUS; * Patients who cannot take or refuse to take adalimumab; * Patients with active or latent tuberculosis; * Patients who have had systemic antibiotic, antiviral or antifungal treatment(s) within 3 weeks prior to Screening for all non-Crohn's related infections; * Patients concurrently taking anakinra (Kineret); * Patients with a history of cancer or lymphoproliferative disease other than a successfully and completely treated cutaneous squamous cell or basal cell carcinoma or carcinoma in-situ of the cervix; * Patients with chronic hematologic problems such as bleeding dyscrasias; * Patients with a history of demyelinating disease (i.e. multiple sclerosis); and * Patients with congestive heart failure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Durable Fistula Healing | at week 48 | Complete cessation of fistula drainage at 48 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Disease Activity | Baseline and 48 Weeks | Changes in Crohn's disease activity using the Harvey Bradshaw Index (HBI) at Week 48 compared to baseline HBI Scores. Higher numbers for the HBI equal more significant disease activity. Range can vary from 0 to 17 plus the number of liquid stools per day. |
| Changes in Perianal Disease Activity Index (PDAI) | Baseline and 48 Weeks | Changes in Crohn's disease activity at Week 48 compared to baseline based on PDAI Scores- higher numbers equal more significant disease activity. PDAI has a range from 0 to 20. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adalimumab With EUS Guided Therapy Patients will be randomized to adalimumab treatment with EUS guided therapy decisions. Colorectal surgeon will have access to EUS data prior to EUA with possible seton placement. | 9 |
| Adalimumab Patients will be randomized to adalimumab treatment. Colorectal surgeon will not have access to EUS data prior to EUA with possible seton placement. | 11 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Adalimumab With EUS Guided Therapy | Adalimumab | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 11 Participants | 20 Participants |
| Region of Enrollment United States | 9 participants | 11 participants | 20 participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 9 | 1 / 11 |
| serious Total, serious adverse events | 0 / 9 | 0 / 11 |
Outcome results
Primary
Number of Participants With Durable Fistula Healing
Complete cessation of fistula drainage at 48 weeks
Time frame: at week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Adalimumab With EUS Guided Therapy | Number of Participants With Durable Fistula Healing | 7 participants |
| Adalimumab | Number of Participants With Durable Fistula Healing | 8 participants |
Secondary
Changes in Disease Activity
Changes in Crohn's disease activity using the Harvey Bradshaw Index (HBI) at Week 48 compared to baseline HBI Scores. Higher numbers for the HBI equal more significant disease activity. Range can vary from 0 to 17 plus the number of liquid stools per day.
Time frame: Baseline and 48 Weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Adalimumab With EUS Guided Therapy | Changes in Disease Activity | -5.0 units on a scale |
| Adalimumab | Changes in Disease Activity | -1.0 units on a scale |
Secondary
Changes in Perianal Disease Activity Index (PDAI)
Changes in Crohn's disease activity at Week 48 compared to baseline based on PDAI Scores- higher numbers equal more significant disease activity. PDAI has a range from 0 to 20.
Time frame: Baseline and 48 Weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Adalimumab With EUS Guided Therapy | Changes in Perianal Disease Activity Index (PDAI) | -5.50 units on a scale |
| Adalimumab | Changes in Perianal Disease Activity Index (PDAI) | -5.0 units on a scale |