TDM Guided Early Optimization of ADAL in Crohn's Disease
- Conditions
- Crohn DiseaseInflammatory Bowel DiseasesDrug Monitoring
- Interventions
- Registration Number
- NCT03261102
- Lead Sponsor
- waqqas.afif
- Brief Summary
To investigate the influence of early therapeutic drug monitoring and dose optimization on disease outcome in Crohn's patients treated with Adalimumab.
- Detailed Description
This is an investigator initiated randomized open label study. This study is designed to compare whether increasing the dose of adalimumab based on the level the drug in the blood to a target level early in the treatment course would lead to better outcomes for patients as compared to the standard doses.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 200
- Age 18 or older.
- Crohn's disease diagnosed based on standard objective methodology (clinical, biochemical, endoscopic, histological and radiological correlation).
- Active disease based on Harvey Bradshaw Index (HBI >5) and elevated C-reactive protein (CRP) (>normal reference range for local laboratory) OR fecal calprotectin (FCP) (>250 µg/g)
- Due to commence treatment with ADAL.
- Severe co-existing cardiopulmonary, hepatic, renal, neurologic, or rheumatologic disease.
- History of active HIV, hepatitis B or C infection,
- Patients with ileostomy/colostomy, ileal-pouch anal anastomosis or severe perianal fistulising disease.
- Pregnancy
- Prior exposure to ADAL
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard clinical care Adalimumab Adalimumab induction as per standard clinical care: * Week 0: 160 mg SC * Week 2: 80 mg SC * Followed by 40 mg SC every 2 weeks' maintenance therapy Active optimization Adalimumab Same as Standard clinical care Arm, except: * If ADAL trough ≤15 μg/ml, dose escalation with 80 mg SC at week 6 followed by 40 mg SC every week * If ADAL trough \>15 μg/ml, no dose escalation and continued standard of care dosing
- Primary Outcome Measures
Name Time Method Proportion of subjects who achieved remission Week 12 Clinical remission will be scored by a Harvey-Bradshaw Index \< 5 AND Biochemical remission will be scored by C-reactive protein \< 5 mg/l OR Fecal calprotectin \<250 μg/g (combination endpoint)
- Secondary Outcome Measures
Name Time Method Proportion of steroid free subjects At Week 12 Steroid free defined as patients being steroid free at Week 12
Rates of complications 12 weeks Rates of complications, including hospitalization, surgery, adverse reaction, and corticosteroid use.
Proportion of subjects who achieved clinical response From Week 0 to Week 12 Clinical response will be evaluated by a decreased in Harvey-Bradshaw Index score AND a decreased level of C-reactive protein OR Fecal calprotectin
Subjects well-being From Week 0 to Week 12 Subjects well-being will be scored using the validated questionnaire Short inflammatory bowel disease questionnaire (SIBDQ)
Therapeutic drug monitoring At Week 8, 12 Adalimumab drug concentration at week 8 and 12 AND proportion of subjects with antibody to Adalimumab at Week 8 and 12 on the rate i. Clinical response/remission (HBI\<5) ii. Biochemical response/remission (CRP within normal reference range) iii. Endoscopic response (SES-CD reduction of ≥50% from baseline) / remission (SES-CD ≤3)
Trial Locations
- Locations (6)
University of Calgary Medical Center (UCMC)
🇨🇦Calgary, Alberta, Canada
The University of British Columbia
🇨🇦Vancouver, British Columbia, Canada
London Health Sciences Centre (LHSC) University Hospital
🇨🇦London, Ontario, Canada
The Ottawa Hospital, IBD Centre of Excellence
🇨🇦Ottawa, Ontario, Canada
McGill University Hospital Center (MUHC)
🇨🇦Montréal, Quebec, Canada
Centre Hospitalier Universitaire de Sherbrooke (CHUS)
🇨🇦Sherbrooke, Quebec, Canada