Corticosteroid Dosage for Crohn's Disease Flare

• Sponsor: Yale University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02392286
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arms: 2
• Actual Duration (Months): 21.7
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Crohn's Disease; Inflammatory Bowel Disease	Drug: Corticosteroid	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized Trial Comparing the Efficacy of Body-weight Based Versus Fixed Corticosteroid Dosage on Remission in Patients With Moderate to Severe Crohn's Disease Flares
• Actual Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Dec 19, 2016
• Actual Study Completion Date: Dec 19, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Weight-based Corticosteroid dose weight-based at equivalent to 1mg/kg prednisone daily.	Drug: Corticosteroid; Subjects will receive prednisone orally; if intravenous corticosteroid required initially they will receive methylprednisolone for the first 3-4 days of therapy.; Other Names: Prednisone Methylprednisolone
Active Comparator: Fixed dose Corticosteroid dose fixed at equivalent to 40mg prednisone daily.	Drug: Corticosteroid; Subjects will receive prednisone orally; if intravenous corticosteroid required initially they will receive methylprednisolone for the first 3-4 days of therapy.; Other Names: Prednisone Methylprednisolone

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. 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

3. 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

4. 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

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale-New Haven Hospital	New Haven	Connecticut	United States	06510

Sponsors and Collaborators

• Yale University

Investigators

• Principal Investigator: Loren Laine, MD, Yale University, Section of Digestive Diseases

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT02392286
• Other Study ID Numbers: 1501015143
• First Posted: Mar 18, 2015
• Last Update Posted: Aug 9, 2021
• Last Verified: Aug 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Yale University: Corticosteroid
• Additional relevant MeSH terms: Crohn Disease; Inflammatory Bowel Diseases; Prednisone; Methylprednisolone

Study Results

Participant Flow

Arm/Group Title	Weight-based	Fixed Dose
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	7	8
COMPLETED	4	6
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Weight-based	Fixed Dose	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	7	8	15
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 71.4%	6 75%	11 73.3%
>=65 years	2 28.6%	2 25%	4 26.7%
Sex: Female, Male (Count of Participants)
Female	3 42.9%	4 50%	7 46.7%
Male	4 57.1%	4 50%	8 53.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 14.3%	0 0%	1 6.7%
Not Hispanic or Latino	6 85.7%	8 100%	14 93.3%
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	0 0%	1 12.5%	1 6.7%
White	7 100%	7 87.5%	14 93.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	7 100%	8 100%	15 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants in Remission at End of 2 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

1 patient in fixed dose group did not return for this assessment.

Arm/Group Title	Weight-based	Fixed Dose
Arm/Group Description	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.	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.
Measure Participants	7	7
Count of Participants [Participants]	2 28.6%	3 37.5%

2. Secondary Outcome

Title	Number of Participants With Response at End of 2 Weeks
Description	Number of participants with at least a 3-point drop in Harvey-Bradshaw Index at end of 2 weeks
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

1 patient in fixed-dose group did not return for this assessment.

Arm/Group Title	Weight-based	Fixed Dose
Arm/Group Description	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.	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.
Measure Participants	7	7
Count of Participants [Participants]	4 57.1%	6 75%

3. Secondary Outcome

Title	Number of Participants With Response or Remission at End of 1 Week
Description	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

Outcome Measure Data

Analysis Population Description

1 patient in weight-based group and 2 patients in fixed-dose group did not return for this assessment.

Arm/Group Title	Weight-based	Fixed Dose
Arm/Group Description	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.	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.
Measure Participants	6	6
Count of Participants [Participants]	5 71.4%	5 62.5%

4. Secondary Outcome

Title	Number of Participants With Response or Remission at End of 4 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

2 patients in weight-based group and 1 patient in fixed-dose group did not return for this assessment.

Arm/Group Title	Weight-based	Fixed Dose
Arm/Group Description	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.	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.
Measure Participants	5	7
Count of Participants [Participants]	5 71.4%	5 62.5%

5. Secondary Outcome

Title	Number of Participants With Response or Remission at End of 12 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

1 patient in fixed-dose group did not return for this assessment.

Arm/Group Title	Weight-based	Fixed Dose
Arm/Group Description	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.	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.
Measure Participants	7	7
Count of Participants [Participants]	5 71.4%	7 87.5%

6. Secondary Outcome

Title	Number of Participants With Corticosteroid-associated Side Effects
Description	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

Outcome Measure Data

Analysis Population Description

1 patient in fixed dose did not return and did not have any assessment for this outcome after randomization.

Arm/Group Title	Weight-based	Fixed Dose
Arm/Group Description	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.	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.
Measure Participants	7	7
Count of Participants [Participants]	5 71.4%	7 87.5%

Adverse Events

Time Frame	Up to 12 weeks.
Arm/Group Title	Weight-based		Fixed Dose
Arm/Group Description	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.		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.
All Cause Mortality
	Weight-based		Fixed Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/8 (0%)
Serious Adverse Events
	Weight-based		Fixed Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)		4/8 (50%)
Gastrointestinal disorders
Hospitalization for Crohn's disease	1/7 (14.3%)		4/8 (50%)
Other (Not Including Serious) Adverse Events
	Weight-based		Fixed Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/7 (71.4%)		7/8 (87.5%)
Endocrine disorders
Edema	1/7 (14.3%)		3/8 (37.5%)
Musculoskeletal and connective tissue disorders
Myalgia	3/7 (42.9%)		1/8 (12.5%)
Psychiatric disorders
Mood swings	2/7 (28.6%)		5/8 (62.5%)
Sleep disturbance	4/7 (57.1%)		3/8 (37.5%)
Skin and subcutaneous tissue disorders
Acne	2/7 (28.6%)		1/8 (12.5%)
Bruising	1/7 (14.3%)		3/8 (37.5%)

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.