Crohn's Disease, Inflammatory Bowel Disease
Conditions
Keywords
Corticosteroid
Brief summary
Prospective randomized comparative effectiveness trial designed to compare fixed dosing and weight-based dosing of corticosteroids in patients with Crohn's disease flares.
Detailed description
* Determine if weight-based corticosteroid (1mg/kg daily) induces remission at a greater rate than fixed corticosteroid dosage. * Determine if weight-based corticosteroid is associated with greater rate of adverse events than fixed corticosteroid dosage.
Interventions
DRUGCorticosteroid
Subjects will receive prednisone orally; if intravenous corticosteroid required initially they will receive methylprednisolone for the first 3-4 days of therapy.
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age ≥ 18 * Established diagnosis of Crohn's disease * Diagnosis of Crohn's flare * Decision by treating gastroenterologist to start corticosteroid therapy
Exclusion criteria
* Patients in whom corticosteroid therapy is contraindicated: immunocompromised (active cancer on chemotherapy or radiation treatment), severe liver disease (decompensated cirrhosis, active alcoholic hepatitis), end-stage renal disease on dialysis, AIDS or AIDS-defining illness; myocardial infarction within the past year; NYHA Class 4 heart failure * Patients on systemic corticosteroid therapy currently or within the past 8 weeks * Patients not on stable doses of immunomodulators or biologics for at least 8 weeks * Infectious colitis (e.g., C. difficile, CMV, HSV) * Systemic infections (bacteremia, fungal infections) * Fulminant Crohn's disease * Patients who require imminent surgery * Abscess * Pregnancy * Weight \<35 kg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in Remission at End of 2 Weeks | 2 weeks | Number of participants with Harvey Bradshaw Index \< 5 at end of 2 weeks. The minimum score obtainable is 0, suggesting absence of disease or remission, while the maximum score obtainable goes beyond 18 points, depending on the number of stools the patient identifies per day (because 1 point is given for each stool in a day, there is no specific maximum score. A higher score represents more severe disease. \<5 is determined to be remission. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Response at End of 2 Weeks | 2 weeks | Number of participants with at least a 3-point drop in Harvey-Bradshaw Index at end of 2 weeks |
| Number of Participants With Response or Remission at End of 1 Week | 1 week | Number of participants with Harvey-Bradshaw Index \<5 or with a drop in Harvey-Bradshaw Index of at least 3 points at end of 1 week |
| Number of Participants With Response or Remission at End of 4 Weeks | 4 weeks | Number of participants with Harvey-Bradshaw Index \<5 or with a drop in Harvey-Bradshaw Index of at least 3 points at end of 4 weeks |
| Number of Participants With Response or Remission at End of 12 Weeks | 12 weeks | Number of participants with Harvey-Bradshaw Index \<5 or with a drop in Harvey-Bradshaw Index of at least 3 points at end of 12 weeks |
| Number of Participants With Corticosteroid-associated Side Effects | 12 weeks | Number of participants with side effects that may be associated with use of corticosteroids such as mood swings, sleep disturbance, edema, acne, bruising, myalgias. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Weight-based Corticosteroid dose weight-based at equivalent to 1mg/kg prednisone daily.
Corticosteroid: Subjects will receive prednisone orally; if intravenous corticosteroid required initially they will receive methylprednisolone for the first 3-4 days of therapy. | 7 |
| Fixed Dose Corticosteroid dose fixed at equivalent to 40mg prednisone daily.
Corticosteroid: Subjects will receive prednisone orally; if intravenous corticosteroid required initially they will receive methylprednisolone for the first 3-4 days of therapy. | 8 |
| Total | 15 |
Baseline characteristics
| Characteristic | Weight-based | Fixed Dose | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 6 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 8 Participants | 14 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 | 0 Participants | 1 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 | 7 Participants | 7 Participants | 14 Participants |
| Region of Enrollment United States | 7 participants | 8 participants | 15 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 8 |
| other Total, other adverse events | 5 / 7 | 7 / 8 |
| serious Total, serious adverse events | 1 / 7 | 4 / 8 |
Outcome results
Primary
Number of Participants in Remission at End of 2 Weeks
Number of participants with Harvey Bradshaw Index \< 5 at end of 2 weeks. The minimum score obtainable is 0, suggesting absence of disease or remission, while the maximum score obtainable goes beyond 18 points, depending on the number of stools the patient identifies per day (because 1 point is given for each stool in a day, there is no specific maximum score. A higher score represents more severe disease. \<5 is determined to be remission.
Time frame: 2 weeks
Population: 1 patient in fixed dose group did not return for this assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Weight-based | Number of Participants in Remission at End of 2 Weeks | 2 Participants |
| Fixed Dose | Number of Participants in Remission at End of 2 Weeks | 3 Participants |
Secondary
Number of Participants With Corticosteroid-associated Side Effects
Number of participants with side effects that may be associated with use of corticosteroids such as mood swings, sleep disturbance, edema, acne, bruising, myalgias.
Time frame: 12 weeks
Population: 1 patient in fixed dose did not return and did not have any assessment for this outcome after randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Weight-based | Number of Participants With Corticosteroid-associated Side Effects | 5 Participants |
| Fixed Dose | Number of Participants With Corticosteroid-associated Side Effects | 7 Participants |
Secondary
Number of Participants With Response at End of 2 Weeks
Number of participants with at least a 3-point drop in Harvey-Bradshaw Index at end of 2 weeks
Time frame: 2 weeks
Population: 1 patient in fixed-dose group did not return for this assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Weight-based | Number of Participants With Response at End of 2 Weeks | 4 Participants |
| Fixed Dose | Number of Participants With Response at End of 2 Weeks | 6 Participants |
Secondary
Number of Participants With Response or Remission at End of 12 Weeks
Number of participants with Harvey-Bradshaw Index \<5 or with a drop in Harvey-Bradshaw Index of at least 3 points at end of 12 weeks
Time frame: 12 weeks
Population: 1 patient in fixed-dose group did not return for this assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Weight-based | Number of Participants With Response or Remission at End of 12 Weeks | 5 Participants |
| Fixed Dose | Number of Participants With Response or Remission at End of 12 Weeks | 7 Participants |
Secondary
Number of Participants With Response or Remission at End of 1 Week
Number of participants with Harvey-Bradshaw Index \<5 or with a drop in Harvey-Bradshaw Index of at least 3 points at end of 1 week
Time frame: 1 week
Population: 1 patient in weight-based group and 2 patients in fixed-dose group did not return for this assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Weight-based | Number of Participants With Response or Remission at End of 1 Week | 5 Participants |
| Fixed Dose | Number of Participants With Response or Remission at End of 1 Week | 5 Participants |
Secondary
Number of Participants With Response or Remission at End of 4 Weeks
Number of participants with Harvey-Bradshaw Index \<5 or with a drop in Harvey-Bradshaw Index of at least 3 points at end of 4 weeks
Time frame: 4 weeks
Population: 2 patients in weight-based group and 1 patient in fixed-dose group did not return for this assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Weight-based | Number of Participants With Response or Remission at End of 4 Weeks | 5 Participants |
| Fixed Dose | Number of Participants With Response or Remission at End of 4 Weeks | 5 Participants |