AGA INSTITUTE Late Breaking Abstracts Submitted to DDW 2008 These abstracts were presented at Digestive Disease Week ® in San Diego, California, May 17–22, 2008 A Computer-Assisted Personalized Sedation System to Administer Propofol Versus Standard-of-Care Sedation for Colonoscopy and Esophagogastroduodenoscopy: A 1,000-Subject Randomized, Controlled, Multicenter, Pivotal Trial Daniel J. Pambianco, Ronald E. Pruitt, Robert Hardi, Michael L. Weinstein, William C. Bray, Valli P. Kodali, John J. Vargo, Timothy Schubert Background: The SEDASYS System (SS) is an investigational, computer- assisted, personalized sedation system intended to provide endoscopist/nurse teams an “on-label” method to administer propofol sedation for colonoscopy and esophagogastroduodenoscopy (EGD) procedures. This institutional review board-approved study was designed to compare sedation with the SS to the current standard of care (CSC) with midazolam in combination with fentanyl or meperidine. Methods: One thousand subjects (496 SS; 504 CSC) were sedated for 731 colonoscopy and 279 EGDs at 8 sites. Electronic data were captured on a laptop computer. Subject responsiveness was assessed using a Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale. The primary endpoint was area under the curve (AUC) of oxygen desaturation (SpO 2  90%; Table 1). Secondary endpoints were clinician satisfaction with sedation instru- ment, patient satisfaction with sedation instrument, time to recover from se- dation (scope-out until return to MOAA/S = 5) and duration of deep sedation/ general anesthesia (count of MOAA/S = 1 or 0 during procedure). Results: One thousand subjects were randomized into the study. SS subjects received propo- fol (mean, 106.2  57.1 mg colonoscopy; 70.1  37.1 EGD) via a variable rate infusion and a single dose of fentanyl as a premedication (mean, 74.0  23.1 g colonoscopy; 65.6  22.4 EGD). CSC subjects received midazolam (8 sites; mean, 4.8  2.2 mg colonoscopy; 4.3  2.1 EGD) plus fentanyl (5 sites; mean, 98.3  31.1 g colonoscopy; 68.5  24.2 EGD) or meperidine (3 sites; mean, 43.9  15.8 mg colonoscopy; 42.3  15.5 EGD). Table 1 summarizes the results for the primary and secondary endpoints. There were 34 adverse events, 0 serious adverse events, and 0 rescue interventions in the SS arm of the study, compared with 48, 1, and 1 in CSC. Conclusion: In this study physician/ nurse teams were able to safely and effectively administer propofol sedation with the SS during colonoscopy and EGD procedures. SS subjects had signifi- cantly lower AUC for oxygen desaturation compared with CSC subjects. Both physicians and subjects were more satisfied with the sedation achieved with the SS. SS subjects were minimally/moderately sedated, recovered quickly, and had minimal AEs. Asimadoline in the Treatment of Irritable Bowel Syndrome Allen W. Mangel, Jeffrey Bornstein, Lynne Hamm, Jeff Buda, Jianmin Wang, William Irish, David Urso Introduction: Asimadoline is a selective and potent peripherally restricted -opi- oid agonist. Preclinical and clinical pharmacology evaluations suggest potential utility in the treatment of irritable bowel syndrome (IBS). We evaluated asim- adoline in a large, randomized, placebo-controlled, dose-ranging study in IBS patients. Methods: Diarrhea-predominant (D-IBS), constipation-predominant (C- IBS), and alternating IBS (A-IBS) patients were recruited from 100 US sites. Patients underwent a 2-week screening period followed by 12 weeks of treat- ment and a 4-week follow-up period. Randomized patients received identical- appearing placebo, 0.15-, 0.5-, or 1.0-mg tablets BID for the treatment period. Patients entered data daily using an interactive voice response system. The primary efficacy endpoint was number of months a patient was a responder for adequate relief: “In the past 7 days have you had adequate relief of your IBS pain or discomfort?” A monthly responder replied “yes” 3 weeks out of 4. Secondary endpoints included abdominal pain, stool frequency and consis- tency, urgency, bloating, adequate relief of IBS symptoms, and straining. Ad- verse events (AE), laboratory values, and electrocardiographs were collected. Results: Five hundred ninety-six patients were randomized. Approximately 33% of patients were characterized as D-IBS, 37% C-IBS, and 31% A-IBS. In patients with at least moderate pain, a 17% (40% vs 23%) improvement in percent number of months with adequate relief was seen for both 0.5 mg (P = .006) and 1.0 mg (P = .005) asimadoline. Evaluation by IBS subtype revealed benefit in D-IBS and A-IBS patients, but not in C-IBS. In D-IBS, a significant increase in percent months with adequate relief was seen with 0.5 mg (47% vs 20%; P = .011) as compared with placebo, and in A-IBS with 1.0 mg (50% vs 27%; P = .022) as compared with placebo. In D-IBS, a statistically significant (P  .05) improvement in urgency, adequate relief of IBS symptoms, stool frequency, bloating, and daily pain was seen with the 0.5-mg dose. Approximately 25% (20 days) more pain-free days were seen with asimadoline as compared with placebo (P = .001). Benefit was seen in both female and male patients. Rates of AEs were similar across all 4 arms. Discussion: Asimadoline produced significant improvement in D-IBS across multiple parameters, including pain, urgency, frequency, and bloating. Effects occurred during the first month of treatment and persisted for the duration of treatment. Benefit was also seen in A-IBS patients. Asimadoline seemed to be well tolerated. Asimadoline shows an encouraging safety and efficacy profile in D-IBS and A-IBS patients. The study was sponsored by Tioga Pharmaceuticals, Inc. A Randomized Trial of Methotrexate in Combination With Infliximab for the Treatment of Crohn’s Disease Brian Feagan, John W. McDonald, Remo Panaccione, Robert A. Enns, Charles N. Bernstein, Terry P. Ponich, Raymond Bourdages, Donald G. MacIntosh, Chrystian Dallaire, Albert Cohen, Richard Fedorak, Pierre Pare, Alain Bitton, Fred Saibil, Frank Anderson, Allan Donner, Cindy J. Wong, Guang Yong Zou, Margaret Vandervoort, Marybeth Hopkins, Gordon R. Greenberg Both methotrexate (MTX) and infliximab (IFX) are effective therapies for active Crohn’s disease (CD); however, it is unknown whether the combination is superior to IFX alone. Methods: We conducted a 50-week, double-blind, multi- center, controlled trial that compared combination therapy to IFX alone in patients with active CD. Eligible patients had initiated prednisone induction therapy within 6 weeks. Patients previously treated with IFX and those at risk for MTX or IFX toxicity were excluded. Patients were randomly assigned to receive MTX 25 mg subcutaneously weekly or placebo (PBO). Both groups received IV Table 1. Clinical Endpoints Colonoscopy EGD SS (n = 358) CSC (n = 363) SS (n = 138) CSC (n = 141) Mean AUC (% * sec) 17.8† (0–1741) 98.8 (0–7040) 38.6† (0–1771) 60.2 (0–996) CSSI (0–100) 92.4† (27.1–100) 75.8 (25.0–100) 92.1† (35.4–100) 77.0 (42.7–100) PSSI (0–100) 92.5‡ (0–100) 90.5 (35.4–100) 91.0* (24.0–100) 87.9 (39.6–100) Time to recovery (min) 2.7† (0–15) 6.3 (0–37) 3.5† (0–12) 7.0 (0–36) Deep sedation/general anesthesia (min) 0.1** (0–16) 0.1 (0–22) 0.0*** (0–4) 0.1 (0–10) AUC, area under the curve; CSC, current standard of care; CSSI, clinician satisfaction with sedation instrument; EGD, esophagogastroduode- noscopy; PSSI, patient satisfaction with sedation instrument; SS, SEDASYS System. † P  .001; ‡ P = .036; *P  .084; **P  .573; ***P  .731. AGA INSTITUTE GASTROENTEROLOGY 2008;135:294 –296