Lubiprostone Compared to Senna in the Treatment of Postoperative Opioid-Induced Constipation Following Orthopedic Procedures

Abstract

Purpose: To assess the efficacy of lubiprostone compared to senna on bowel symptoms and bowel-related quality of life in patients undergoing inpatient rehabilitation following orthopedic procedures and who have opioid-induced constipation symptoms. Methods: In this double blind, randomized, active comparator trial, adults admitted to acute rehabilitation following orthopedic procedures exhibiting constipation symptoms and who required opioids for analgesia underwent baseline assessments which included the Patient Assessment of Constipation Symptoms (PAC-SYM) and the Patient Assessment of Constipation - Quality of Life (PAC-QOL) measured at baseline and study exit (Day 7); Secondary Measures included the Bristol Stool Scale Bowel Consistency. Specific Bowel Symptom Score (Nausea, cramping, straining, completeness, abdominal pain, time per lavatory attempt, assistance needed). Participants were randomized to one of two active treatment groups. lubiprostone (Amitza®), 24 μg orally twice a day or senna (generic) two capsules daily administered daily for six days and corresponding placebo tablets. Subjects were followed daily for symptom control, and questionnaires completed at Day seven. Results: Sixty-four adults were enrolled; 58 participants (28 in each group) completed baseline and Day seven assessments and were included in intention to treat (ITT) analyses. Forty-three participants completed the study, 21 in the active lubiprostone and 22 in the active senna group. The mean age of the participants was 71.5 (SD=11.4, range 28-96) years. In the ITT analyses, study participants showed significant improvement in bowel symptoms as measured by the PAC-SYM (mean change ± SD = -0.28±0.60, range -1 to 2.33) and PAC-QOL (mean change ± SD=0.33 ±0.81, range -1.5-2.0) over time, but there were no significant differences between the lubiprostone and senna groups for change in the PAC-SYM (mean change ± SD= -0.20±0.60 and mean change ± SD = -0.36±0.60, respectively) or the PAC-QOL (mean change ± SD=0.29 ±0.76 and mean change ± SD=0.37±0.87, respectively). The mean change in each bowel symptom also did not significantly differ between treatment groups for ITT analyses, nor did PAC-SYM subscales. Fifteen (75%) participants in the lubiprostone and 18 (78.2%) in the senna group requested rescue treatments (P value=1.00). Conclusion: Participants receiving either lubiprostone and senna demonstrated improved constipation-related symptoms and quality of life over the treatment period in the setting of opioid-induced constipation, however there were no significant differences noted between the two treatment groups in the outcomes measured. Despite daily scheduled use of these two laxative interventions, additional laxatives were frequently required for symptom control. Disclosure: Dr. Marciniak's Spouse - consultant Takeda. This research was supported by an industry grant from Takeda Pharmaceuticals.