Stricture Definition and Treatment (STRIDENT) Drug Therapy Study (STRIDENT)

Two thirds of patients with Crohn's disease require intestinal surgery at some time in their life. Intestinal strictures, that is narrowing of the bowel due to inflammation and scarring, are the most common reason for surgery. Despite the high frequency, associated disability, and cost there are no are no treatment strategies that aim to improve the outcome of this disease complication. The STRIDENT (stricture definition and treatment) studies aim to develop such strategies.

Study Overview

• Status: Unknown
• Conditions: Inflammatory Bowel Diseases; Crohn Disease; Stricture; Bowel
• Intervention / Treatment: Drug: Adalimumab Injection; Procedure: Endoscopic balloon dilatation; Drug: Thiopurine

Detailed Description

Prospective randomised controlled study. Patients with Crohn's Disease who have symptomatic inflammatory intestinal strictures will be randomised to receive standard drug therapy (Anti-TNF monotherapy at standard dose) or intensive drug therapy (Intense Anti-TNF dose induction and escalation for continued inflammation in combination with thiopurine) for 12 months.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3065
      • St. Vincent's Hospital Melbourne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Inflammatory bowel disease patients with intestinal stricture(s) identified on CT, MRI or endoscopy.

Exclusion Criteria:

• Acute bowel obstruction requiring urgent surgical intervention
• Deemed by treating physician to have high risk of acute bowel obstruction
• Concurrent active perianal sepsis
• Internal fistulising disease in association with strictures (entero-enteric stulas)
• Low rectal or anal strictures
• Evidence of dysplasia or malignancy from stricture biopsies or adjacent mucosal biopsies
• Patients for whom endoscopy is not suitable due to co-morbidities or clinical state
• Inability to give informed consent
• Suspected perforation of the gastrointestinal tract
• Pregnancy
• Inability to undergo MRI small bowel due to a contraindication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Standard drug therapy; Adalimumab monotherapy, Standard Dose induction (160mg at week 0, 80mg week 2 and 40mg fortnightly thereafter)	Drug: Adalimumab Injection; Standard dose adalimumab induction and maintenance; Procedure: Endoscopic balloon dilatation; Prior to randomization, suitable patients may undergo endoscopic balloon dilatation. Patients undergoing dilatation will be stratified to ensure equal numbers in each study arm.
EXPERIMENTAL: Intensive drug therapy; Adalimumab in combination with dose optimized thiopurine, Intensive induction (160mg weekly for 4 weeks then 40mg fortnightly). Anti-TNF dose may be increased if ongoing inflammation every 4 months until study endpoint.	Drug: Adalimumab Injection; Standard dose adalimumab induction and maintenance; Procedure: Endoscopic balloon dilatation; Prior to randomization, suitable patients may undergo endoscopic balloon dilatation. Patients undergoing dilatation will be stratified to ensure equal numbers in each study arm.; Drug: Thiopurine; Dose optimized thiopurine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in obstructive symptoms.	Improved pain and or frequency of pain compared to baseline. Obstructive symptoms determined by prospective diary documenting number of episodes of pain in previous 2 weeks and severity of the pain episodes using four-level Likert scale.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in symptoms	Improved pain and or frequency of pain compared to baseline. Obstructive symptoms determined by prospective diary documenting number of episodes of pain in previous 2 weeks and severity of the pain episodes using four-level Likert scale.	4, 8 and 12 months
Improvement in biochemical inflammatory parameters	Serum CRP and fecal calprotectin	12 months
Improvement in imaging parameters (Intestinal ultrasound)	Limberg's score	12 months
Improvement in imaging parameters	Modified MaRIA score	12 months
Surgery	The number of patients that require surgical resection of stricture due to failure of drug therapy.	12 months
Improvement in patient reported outcomes (PROs)	SF36	12 months
Improvement in patient reported outcomes (PROs)	IBDQ	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Failure	Number of patients who drop out of the study because of clinical symptoms, acute bowel obstruction, unscheduled endoscopic or surgical intervention.	12 months

Collaborators and Investigators

• Sponsor: St Vincent's Hospital Melbourne
• Collaborators: AbbVie; Australasian Gastro Intestinal Research Foundation

Publications and helpful links

General Publications

• Schulberg JD, Wright EK, Holt BA, Hamilton AL, Sutherland TR, Ross AL, Vogrin S, Miller AM, Connell WC, Lust M, Ding NS, Moore GT, Bell SJ, Shelton E, Christensen B, De Cruz P, Rong YJ, Kamm MA. Intensive drug therapy versus standard drug therapy for symptomatic intestinal Crohn's disease strictures (STRIDENT): an open-label, single-centre, randomised controlled trial. Lancet Gastroenterol Hepatol. 2022 Apr;7(4):318-331. doi: 10.1016/S2468-1253(21)00393-9. Epub 2021 Dec 8.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 9, 2017
• Primary Completion (ACTUAL): September 18, 2020
• Study Completion (ANTICIPATED): September 1, 2021

Study Registration Dates

• First Submitted: July 6, 2017
• First Submitted That Met QC Criteria: July 13, 2017
• First Posted (ACTUAL): July 18, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 23, 2020
• Last Update Submitted That Met QC Criteria: October 22, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Inflammatory Bowel Disease; Crohn Disease; Intestinal stricture
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Pathological Conditions, Anatomical; Inflammatory Bowel Diseases; Crohn Disease; Constriction, Pathologic; Intestinal Diseases; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: StVincentsMelbourneSTRIDENT1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No