Validation of a Patient Satisfaction Scale in Patients Undergoing Bowel Preparation Prior to Colonoscopy.

BACKGROUND: Colonoscopy is the most widely used test to screen for colorectal cancer but its use may be hindered by patients' inability to complete the bowel preparation. Patient-reported satisfaction with bowel-cleansing preparations has received little attention. We assessed the reliability and validity of a patient satisfaction survey used in two large, multicenter, randomized, assessor-blinded colonoscopy trials. METHODS: Datasets from two pivotal trials were combined. Patients in both trials included men and women aged 18-80 years who were scheduled for an elective outpatient colonoscopy. Questions relevant to satisfaction with bowel preparation prior to colonoscopy were identified from the literature and incorporated into a 7-item survey administered to patients on the day of colonoscopy. Domain 1 of the satisfaction measure assessed difficulty using bowel-cleansing preparations, ability to consume preparations, acceptability of taste, and overall experience; questions regarding acceptance or refusal of future use of the same bowel preparation were asked in Domain 2. Responses from each item of Domain 1 were transformed on a scale ranging from 0 to 100 and summed as total satisfaction scores. Cronbach's alpha was used to measure reliability; validity was assessed by evaluating relationship between total satisfaction (Domain 1) and willingness to use preparation in the future (Domain 2). RESULTS: Mean age of the 1211 trial participants was 56: 61 % female, 89.5 % Caucasian. Domain 1 had a Cronbach's alpha of 0.79, with higher satisfaction predicting higher future acceptability (p < 0.0001). CONCLUSION: The patient-reported satisfaction measure of bowel-cleansing preparations possesses good validity and reliability.

Serum magnesium concentrations in patients receiving sodium picosulfate and magnesium citrate bowel preparation: an assessment of renal function and electrocardiographic conduction.

BACKGROUND: We performed a post hoc analysis of two clinical trials to assess whether sodium picosulfate and magnesium (Mg(2+)) citrate (Prepopik(®) [P/MC]), a dual-action bowel preparation for colonoscopy, has an impact on serum Mg(2+) levels and cardiac electrophysiology. Although rare, hypermagnesemia has been reported in patients consuming Mg(2+)-containing cathartics, especially patients who are elderly and have renal impairment. METHODS: Data were analyzed from two prospective, Phase III, randomized, assessor-blinded, active-control, multicenter, pivotal studies that investigated split-dose/day-before P/MC. Serum Mg(2+) and creatinine clearance (CrCl) were measured at screening, on the day of colonoscopy, and 24-48 hours, 7 days, and 4 weeks after colonoscopy; electrocardiograms also were obtained at these time points. RESULTS: In total, 304 patients received split-dose P/MC and 294 patients received day-before P/MC. Only 10% of the patients had serum Mg(2+) above the upper limit of normal (1.05 mmol/L) on the day of colonoscopy. There was a slight inverse correlation between CrCl and Mg(2+) levels on the day of colonoscopy; however, even at the lowest CrCl, serum Mg(2+) remained below clinically significant levels of 2.0 mmol/L. Increases in serum Mg(2+) were transient, with levels returning to baseline within 24-48 hours, regardless of renal function. No patients with elevated Mg(2+) experienced a corrected QT (QTc) interval >500 milliseconds or a QTc interval increase of ≥60 milliseconds from baseline. P/MC had no impact on PR or QRS interval. CONCLUSION: P/MC produces little impact on serum Mg(2+) levels with no clinically significant effect on cardiac conduction in patients, including those with mild-to-moderate renal impairment.

Split-dose administration of a dual-action, low-volume bowel cleanser for colonoscopy: the SEE CLEAR I study.

BACKGROUND: New bowel cleansers for colonoscopy that lead to improved efficacy, safety, and tolerability are needed. OBJECTIVE: This study evaluated a nonphosphate, dual-action, low-volume, orange-flavored preparation containing sodium picosulfate and magnesium citrate (P/MC). DESIGN: Multicenter, assessor-blinded, randomized, noninferiority study. SETTING: University hospitals, academic medical centers, and private clinics across the United States. PATIENTS: Adults preparing for colonoscopy. INTERVENTIONS: P/MC versus 2 L of polyethylene glycol solution (2L PEG-3350) and two 5-mg bisacodyl tablets. MAIN OUTCOME MEASUREMENTS: This phase 3 study investigated the efficacy, safety, and tolerability of split-dose administration of P/MC versus day-before dosing of 2L PEG-3350 and two 5-mg bisacodyl tablets (SEE CLEAR I study). Efficacy was evaluated by using the Aronchick and Ottawa scales; noninferiority and superiority analyses were performed. Safety was assessed by monitoring adverse events (AEs). Tolerability was measured via a patient questionnaire. RESULTS: The intent-to-treat population consisted of 601 patients who self-administered P/MC (n = 304) or 2L PEG-3350 and bisacodyl tablets (n = 297). P/MC was superior to 2L PEG-3350 and bisacodyl tablets in overall colon cleansing (84.2% vs 74.4%; 1-sided 97.5% confidence interval [CI], 3.4) (Aronchick scores of excellent or good) and in cleansing of the ascending (89.5% vs 78.8%; 1-sided 97.5% CI, 4.9), mid (transverse and descending) (92.4% vs 85.9%; 1-sided 97.5% CI, 1.6), and rectosigmoid (92.4% vs 87.2%; 1-sided 97.5% CI, 0.4) segments of the colon (Ottawa scores of excellent, good, or fair). Commonly reported AEs related to the bowel preparations were nausea, vomiting, headache, and chills. Patient-reported tolerability, including ease of consumption and taste, was significantly higher for P/MC than 2L PEG-3350 and bisacodyl tablets (P < .0001). LIMITATIONS: Because of differences in administration and volume of the bowel preparations, the study was designed to be a single-assessor, blinded study. CONCLUSIONS: The bowel-cleansing effects and patient acceptability of split-dose P/MC were superior to day-before dosing with 2L PEG-3350 and bisacodyl tablets.

A dual-action, low-volume bowel cleanser administered the day before colonoscopy: results from the SEE CLEAR II study.

OBJECTIVES: Optimal bowel preparation is vital for the efficacy and safety of colonoscopy. The inconvenience, discomfort, required consumption of large volumes of product, and potential adverse effects associated with some bowel preparations deter patients from colonoscopy and may provide inadequate cleansing. A dual-action, non-phosphate, natural orange-flavored, low-volume preparation containing sodium picosulfate and magnesium citrate (P/MC) is currently being reviewed for bowel cleansing. METHODS: This was a phase 3, randomized, multicenter, assessor-blinded, prespecified non-inferiority, head-to-head study to investigate the efficacy, safety, and tolerability of day-before administration of P/MC vs. 2L polyethylene glycol solution and two 5-mg bisacodyl tablets (2L PEG-3350 and bisacodyl tablets (HalfLytely and Bisacodyl Tablets Bowel Prep Kit)) in adult patients preparing for colonoscopy (SEE CLEAR II Study). The primary objective of the study was to demonstrate the non-inferiority of P/MC to 2L PEG-3350 and bisacodyl tablets in overall colon cleansing using a modified Aronchick scale. In addition, efficacy in the ascending, mid (transverse and descending), and recto-sigmoid segments of colon was evaluated using a modified Ottawa scale. Patient acceptability and tolerability of the bowel preparations were assessed via a standard questionnaire. Safety was assessed based on the monitoring of adverse events (AEs) and meaningful findings on clinical evaluations including physical examinations, vital sign measurements, and electrocardiograms (ECGs). RESULTS: A total of 603 patients were randomized to receive either P/MC (n = 300) or 2L PEG-3350 and bisacodyl tablets (n = 303). Based on the Aronchick scale, successful overall cleansing was similar in patients receiving P/MC (83.0%) and patients receiving 2L PEG-3350 and bisacodyl tablets (79.7%). P/MC demonstrated non-inferiority to 2L PEG-3350 and bisacodyl tablets in overall cleansing of the colon, as measured by the Aronchick scale. Similarly, the efficacy of P/MC, as measured by the Ottawa scale, was non-inferior to 2L PEG-3350 and bisacodyl tablets in cleansing the ascending, mid, and recto-sigmoid segments of the colon. Patient-reported acceptability and tolerability for each item examined on the questionnaire was significantly greater for P/MC compared with 2L PEG-3350 and bisacodyl tablets (P<0.0001).Treatment-emergent AEs related to the bowel preparation reported by 1% of patients receiving P/MC or 2L PEG-3350 and bisacodyl tablets were nausea (3.0% vs. 4.3%), vomiting (1.4% vs. 2.0%), and headache (2.7% vs. 1.7%). No clinically meaningful changes were noted in either treatment arm in data collected from physical examinations, vital sign measurements, and ECGs. CONCLUSIONS: When administered as a day-before dose, the bowel cleansing effects of P/MC were non-inferior compared with 2L PEG-3350 and bisacodyl tablets using the clinician-rated Aronchick and Ottawa scales. Treatment acceptability was significantly more favorable in patients receiving P/MC than in patients receiving 2L PEG-3350 and bisacodyl tablets.

Expanding applications: the potential usage of 5-aminosalicylic acid in diverticular disease.

Diverticular disease is a common bowel condition, the pathogenesis of which is incompletely understood. Acute exacerbations of diverticular disease usually require dietary changes, antibiotic therapy, and may necessitate urgent surgery. Approximately 25-33% of patients experience symptomatic and acute inflammatory disease recurrence, suggesting that current long-term management is inadequate. Because inflammatory complications of diverticular disease, including diverticulitis, are similarities to inflammatory bowel diseases, evidence suggests that patients may respond to anti-inflammatory therapies used in these conditions. Here, we explore the rationale and evidence for use of inflammatory bowel disease treatment, namely 5-aminosalicylic acid (5-ASA; mesalamine), in diverticular disease, and review clinical data on the efficacy of mesalamine either alone or in combination with other agents for the treatment of diverticular disease. PubMed and conference abstracts were searched for clinical studies examining the use of mesalamine in treating diverticular disease. Studies were evaluated for treatment efficacy in symptom reduction, recurrence prevention, or improving quality of life. The results of our search suggest that single-agent mesalamine can reduce diverticular disease symptoms and improve quality of life more effectively than antibiotic treatment alone. Mesalamine in combination with antibiotics can also reduce symptoms and improve quality of life with greater efficacy than either treatment alone. Combining mesalamine and probiotics treatments may reduce recurrent attacks of diverticular disease. Further randomized, well-controlled studies are required for validation; however, it seems that mesalamine is an important agent in future diverticular disease management.

MMX Mesalamine for Induction and Maintenance Therapy in Mild-to-Moderate Ulcerative Colitis.

Two 8-week, randomized, placebo-controlled parent studies, SPD476-301 (by Lichtenstein and associates) and SPD476-302 (by Kamm and colleagues), of MMX Multi Matrix System (MMX) mesalamine have evaluated the induction of remission in ulcerative colitis patients, and a third study has evaluated the maintenance of remission in patients from these parent studies. Here, we examine data only from patients who received MMX mesalamine 2.4 g or 4.8 g daily in these trials. In total, 63.6% of patients (220/346) achieved remission following 8-16 weeks of MMX mesalamine therapy. Among these 220 eligible patients, 218 entered the 12-month maintenance phase, and of this group, 89.9% (196/218) were relapse-free at study end. Overall, 56.6% (196/346) of patients who started MMX mesalamine therapy both achieved and maintained remission for 12 months. The adverse-event profile of MMX mesalamine was similar to the profile of the parent studies' placebo arms at all doses and frequencies. Therefore, the majority of patients with active, mild-to-moderate ulcerative colitis can achieve remission, including complete symptom resolution and mucosal healing, and remain relapse-free for at least 1 year with MMX mesalamine.

Effect of once- or twice-daily MMX mesalamine (SPD476) for the induction of remission of mild to moderately active ulcerative colitis.

BACKGROUND & AIMS: SPD476 (MMX mesalamine), a novel, once-daily mesalamine formulation, uses MMX Multi Matrix System (MMX) technology to delay and extend delivery of active drug throughout the colon. We performed a randomized, double-blind, parallel-group, placebo-controlled, multicenter phase III study in patients with mild to moderately active ulcerative colitis. METHODS: Two hundred eighty patients with mild to moderately active ulcerative colitis received MMX mesalamine 2.4 g/day given twice daily (n = 93), 4.8 g/day given once daily (n = 94), or placebo (n = 93) for 8 weeks. The primary end point was the percentage of patients in clinical and endoscopic remission (modified ulcerative colitis disease activity index score of < or =1, with a score of 0 for rectal bleeding and stool frequency, and at least a 1-point reduction in sigmoidoscopy score) at week 8. Patients with mucosal friability were not considered to have achieved this end point. RESULTS: Clinical and endoscopic remission at week 8 was achieved by 34.1% and 29.2% of patients receiving MMX mesalamine 2.4 g/day given twice daily and MMX mesalamine 4.8 g/day given once daily, respectively, versus 12.9% receiving placebo (P < .01). MMX mesalamine was generally well-tolerated. CONCLUSIONS: MMX mesalamine given once or twice daily is well-tolerated and, compared with placebo, demonstrated efficacy for the induction of clinical and endoscopic remission in mild to moderately active ulcerative colitis.

Once-daily, high-concentration MMX mesalamine in active ulcerative colitis.

BACKGROUND & AIMS: SPD476 (LIALDA in the US; MEZAVANT in the EU; otherwise known as MMX mesalamine; Shire Pharmaceuticals Inc., Wayne, PA, under license from Giuliani SpA, Milan, Italy) is a novel, once-daily, high-strength (1.2 g/tablet) formulation of mesalamine, utilizing MMX Multi Matrix System (MMX) technology designed to deliver the active drug throughout the colon. We performed a double-blind, multicenter study, comparing MMX mesalamine vs placebo for the treatment of active ulcerative colitis. A delayed-release oral mesalamine (ASACOL; Procter & Gamble, Cincinnati, OH) reference arm was included. METHODS: Three hundred forty-three patients with active, mild-to-moderate ulcerative colitis received MMX mesalamine 2.4 g/day or 4.8 g/day given once daily, ASACOL 2.4 g/day given in 3 divided doses, or placebo for 8 weeks. The primary end point was the proportion of patients in clinical and endoscopic remission (modified ulcerative colitis disease activity index of < or =1 with rectal bleeding and stool frequency scores of 0, no mucosal friability, and a > or =1-point reduction in sigmoidoscopy score from baseline). RESULTS: A significantly greater proportion of patients receiving MMX mesalamine 2.4 g/day given once daily (40.5%; P = .01) and 4.8 g/day given once daily (41.2%; P = .007) achieved clinical and endoscopic remission at week 8, vs placebo (22.1%). The clinical and endoscopic remission rate for ASACOL (32.6%; P = .124) was not significantly superior to placebo. All active treatments were well-tolerated. CONCLUSIONS: Once-daily MMX mesalamine was efficacious and well-tolerated for the induction of clinical and endoscopic remission. MMX mesalamine offers effective and convenient mesalamine therapy, potentially improving treatment compliance.