Investigator Initiated Studies

Investigator Initiated Studies

Investigator Initiated Studies

 

Research and Development that drives forward drug development and patient management in inflammatory bowel disease (IBD) is a hallmark that differentiates Alimentiv from other CROs. We tackle important clinical practice questions in IBD that can only be addressed by high-quality evidence from large scale randomized controlled trials. Our physician leaders and collaborators have successfully designed, conducted and executed investigator-initiated clinical trials funded through combinations of industry, charitable and peer-reviewed granting agencies. Some highlights of these endeavours are included below.

 

REACT (Randomized Evaluation of Algorithm for Crohn’s Disease Treatment) Trial

REACT (Principal Investigator: Dr. Brian Feagan), published in the Lancet in 2015, was a large-scale, cluster randomized trial conducted in 41 community practices throughout Canada and Belgium. The trial was funded by Abbvie, with Robarts Clinical Trials as the sponsor. Centers were randomly assigned to follow a treatment algorithm which involved either early combined immunosuppression for consecutive patients presenting with Crohn’s disease (CD) versus continuing with usual care. Although the trial did not find a difference between the two treatment strategies for a symptom-based outcome (Harvey-Bradshaw Index), there was a significant difference between the two treatment strategies after 24 months of follow-up for the outcomes of surgery, hospitalization and complications, providing real-world evidence in support of a treat-to-target approach in the management of patients with CD.

 

REACT-2 Trial

Poor correlation exists between clinical disease activity indices (which rely primarily on symptoms) and objective measures of intestinal inflammation such as endoscopy, and the objective measures are more predictive of disease course. Clinical practice is evolving  to target endoscopic mucosal healing in addition to symptomatic improvement. REACT-2 (Co-principal Investigators: Drs. Brian Feagan and Vipul Jairath), a follow-on to REACT, is a cluster randomized trial conducted in Canada, USA, England and Germany, funded by Abbvie with Robarts Clinical Trials as the sponsor (https://clinicaltrials.gov/ct2/show/NCT01698307). The objective of the REACT-2 trial is to compare the effectiveness of an enhanced algorithm featuring early use of combination therapy with treatment initiation and intensification guided by resolution of endoscopic mucosal ulceration, to a more conventional step-care algorithm in the management of CD. The trial has completed recruitment and is in follow-up phase. Reporting of results is anticipated for early 2021.

 

VERDICT (In actiVE ulcerative colitis, a Randomized Controlled Trial for determination of the optimal treatment target)

Whilst endoscopic mucosal healing is accepted as the treatment goal in ulcerative colitis (UC), this treatment target is not “curative.” Disease relapse nevertheless occurs in patients who meet this outcome despite ongoing therapy. Importantly, histological disease activity persists in approximately one-quarter of patients with normal appearing mucosa and is associated with disease relapse. VERDICT (Principal Investigator: Dr. Vipul Jairath) is a collaborative clinical trial with Takeda pharmaceuticals, with Takeda as the funder and Robarts Clinical Trials as the sponsor (https://clinicaltrials.gov/ct2/show/NCT04259138). Randomization of 660 patients across 10 countries is planned. The primary objective of this trial is to determine whether a treatment target of corticosteroid-free symptomatic, endoscopic AND histological remission is superior to corticosteroid-free symptomatic remission alone for the primary endpoint of time to UC-related complication within 80 weeks of follow-up from achieving the treatment target in patients with moderately-to-severely active UC.

 

STATIC (STopping Aminosalicylate Therapy in Inactive Crohn’s Disease) Trial

Despite limited evidence for their benefit, aminosalicylates are used extensively as a treatment option for induction or maintenance of remission, or for prevention of postoperative recurrence, in patients with CD. STATIC (Principal Investigator: Dr. Vipul Jairath) is a large, simple, randomized, open-label, non-inferiority withdrawal trial. The study is funded by several peer-reviewed grants, with Robarts Clinical Trials as the sponsor (https://clinicaltrials.gov/ct2/show/NCT03261206). The trial is currently recruiting in Canada, England, Ukraine and Italy. Patients with CD in remission will be randomized in a 1:1 ratio to either continue or withdraw aminosalicylate therapy. The primary efficacy evaluation is the non-inferiority of continuing or withdrawing aminosalicylates on any CD‑related complication within 24 months of enrolment.