A Randomized, Placebo-Controlled Phase 3 Trial (Study SB-767905/012) of Alvimopan for Opioid-Induced Bowel Dysfunction in Patients With Non-Cancer Pain

Jansen, Jan-Peter; Lorch, Daniel; Langan, John; Lasko, B.; Hermanns, Kai; Kleoudis, C.; Snidow, Jerry; Pierce, Amy; Wurzelmann, John I.; Mortensen, Eric

doi:10.1016/j.jpain.2010.06.012

Cited by 61 publications

(85 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the definition of Candy and colleagues does neither include the present or recent history of opioid medication nor the change in bowel habits or defecation patterns. Six studies (38%) explicitly mention the present or recent history of opioid therapy in their definition [13][14][15][16]27,28 (Table 3).…”

Section: Definitions For Oicmentioning

confidence: 99%

Definitions and Outcome Measures of Clinical Trials Regarding Opioid-induced Constipation

Gaertner

Siemens

Camilleri

et al. 2015

Journal of Clinical Gastroenterology

View full text Add to dashboard Cite

Opioid-induced constipation (OIC) is a frequent symptom in patients treated with opioids and impacts the patients' quality of life. However, there is no generally accepted definition for OIC. The aims of this study were to identify definitions for OIC in clinical trials and Cochrane Reviews and to compile assessment tools and outcome measures that were used in clinical trials. In a systematic review, 5 databases (MEDLINE, PubMed, The Cochrane Library, Web of Science, and EMBASE) were searched to identify clinical trials assessing OIC in adult patients or healthy volunteers. Studies published between 1993 and August 2013 were included. A total of 1488 studies were retrieved and 47 publications were included in the analysis. A minority of the publications (n=16, 34%) provided a clear definition for OIC. The definitions were highly variable and the present or recent history of opioid therapy was frequently (n=6, 38%) not included in these definitions. Of 46 clinical trials, 17 (37%) relied exclusively on objective measures such as bowel movement frequency, whereas another 17 studies additionally included patient-reported outcome measures such as, "feeling of incomplete bowel evacuation." Few trials (n=7, 15%) assessed the patient-reported global burden of OIC. Standard definitions and outcome measures are necessary (i) for consistency in OIC diagnosis in clinical practice and clinical trials; and (ii) to assure comparability of trial findings (eg, in meta-analyses). An OIC definition and outcome measures are proposed.

show abstract

Section: Definitions For Oicmentioning

confidence: 99%

Definitions and Outcome Measures of Clinical Trials Regarding Opioid-induced Constipation

Gaertner

Siemens

Camilleri

et al. 2015

Journal of Clinical Gastroenterology

View full text Add to dashboard Cite

show abstract

“…This is the first OIC study to evaluate drug efficacy during an RCT and an OLE crossover period, and differences in "responder" definitions prevent comparisons with other studies; however, an RCT of oral μ-opioid receptor antagonist alvimopan that used a definition similar to the one used in the current study (ie, patients who had ≥3 spontaneous bowel movements per week and a mean increase from baseline of ≥1 spontaneous bowel movement per week) showed that responder rates with alvimopan 1 mg/d were only slightly higher (72%) than response rates in the current study. 20 A separate RCT of alvimopan using the identical definition of responder reported no significant difference with alvimopan 1 mg/d compared with placebo. 21 Lower response rates in patients with noncancer pain have been reported with naloxegol (a pegylated μ-opioid receptor antagonist; 34.9%-44.4%) and lubiprostone (a ClC-2 chloride channel agonist, 27.1%), but whether this reflects reduced efficacy or differences in study responder criteria is unknown.…”

Section: Discussionmentioning

confidence: 97%

(451) Efficacy and safety of methylnaltrexone for opioid-induced constipation in patients with chronic noncancer pain: a placebo crossover analysis

Viscusi¹,

Barrett²,

Paterson³

et al. 2014

The Journal of Pain

View full text Add to dashboard Cite

“…The utilization of alvimopan only in patients without significant cardiac conditions, however, has recently come into question. Although there were more reported myocardial infarctions (MIs) in patients treated with alvimopan 0.5 mg twice daily compared to placebo in a 12-month study of patients on chronic opioids for non-cancer pain, this has not been observed in the surgical setting [8,9]. Phase III trials in the patients undergoing bowel resection or TAH have shown similar CV toxicity profiles in alvimopan compared to placebo [10][11][12].…”

Section: Pol Scientificmentioning

confidence: 99%

Clinical utilization patterns of alvimopan in a contemporary cohort of patients undergoing radical cystectomy

Fisher

Zargar‐Shoshtari

Gilbert

et al. 2015

Bladder

View full text Add to dashboard Cite

OBJECTIVE:To evaluate the clinical utilization patterns and outcomes of alvimopan, a peripherally-acting µ-opioid receptor antagonist, after radical cystectomy (RC) and urinary diversion at a high-volume cancer center. PATIENTS AND METHODS:We retrospectively identified 130 consecutive patients who underwent RC and urinary diversion for bladder cancer at our institution from October 2013 to September 2014. Demographic, clinical, and postoperative outcomes were compared between patients who did and did not receive alvimopan using the Kruskal-Wallis test for medians and the chi-square test for proportions. Predictors of 30-day complications and prolonged length of stay (LOS) were analyzed using multivariate logistic regression analysis. RESULTS:Perioperative alvimopan was given to 81 patients (62.3%) during the study period although in 17 patients (13.1%) it was indicated but not given. The most common absolute or relative contraindication for alvimopan usage was prior consumption of opioids for more than 7 consecutive days (n = 18; 13.8%). Patients who received alvimopan had a better performance status (P = 0.06), less comorbidities (P = 0.08), and were more likely to have minimally-invasive surgery (P = 0.07) although these differences did not reach statistical significance. Alvimopan usage was independently associated with less postoperative 30-day complications (odds ratio [OR]: 0.35, 95% confidence interval [CI]: 0.15-0.82; P = 0.015), less high-grade complications (OR: 0.12, 95% CI: 0.044-0.34; P < 0.01), and less prolonged hospitalization > 10 days (OR: 0.28, 95% CI: 0.11-0.72; P = 0.008). CONCLUSIONS:Despite its clinical benefits, alvimopan was under-utilized in RC patients, especially in those with worse baseline health. We recommend its incorporation into standardized protocols to optimize perioperative care.

show abstract

A Randomized, Placebo-Controlled Phase 3 Trial (Study SB-767905/012) of Alvimopan for Opioid-Induced Bowel Dysfunction in Patients With Non-Cancer Pain

Cited by 61 publications

References 15 publications

Definitions and Outcome Measures of Clinical Trials Regarding Opioid-induced Constipation

Definitions and Outcome Measures of Clinical Trials Regarding Opioid-induced Constipation

(451) Efficacy and safety of methylnaltrexone for opioid-induced constipation in patients with chronic noncancer pain: a placebo crossover analysis

Clinical utilization patterns of alvimopan in a contemporary cohort of patients undergoing radical cystectomy

Contact Info

Product

Resources

About