Johanson, J.F., Morton, D., Geenen, J., & Ueno, R. (2008). Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of lubiprostone, a locally-acting type-2 chloride channel activator, in patients with chronic constipation. American Journal of Gastroenterology, 103, 170–177. 

DOI Link

Study Purpose

To assess the efficacy and safety of lubiprostone 24 mcg BID in patients with chronic constipation.

Intervention Characteristics/Basic Study Process

Patients were randomized to receive either oral lubiprostone 24-mcg capsules or placebo capsules. Patients continued to record information regarding bowel movements (BMs), use of rescue medications, and symptoms on a daily basis. Study drug capsules were counted to assess compliance every two weeks. Rescue medication comprised bisacodyl suppository and fleet enema if the suppository was not effective. Efficacy was defined as the frequency of spontaneous BMs during the first and subsequent study weeks. Patients were followed for four weeks.

Sample Characteristics

  • The study reported on a sample of 224 patients.
  • Mean patient age was 48 (SD = 12.28) to 49 years (SD = 12.93) across study groups.
  • The sample was 89% female and 11% male.
  • Patients were excluded if they had mechanical obstruction. No other diagnosis information was provided.

Setting

  • Multi-site
  • Outpatient
  • Midwestern United States

Study Design

This was a double-blind, placebo-controlled randomized trial.

Measurement Instruments/Methods

  • Four-point Likert-type scales for symptoms of bloating, straining, and discomfort; stool consistency; and global treatment effectiveness
  • Patient diary

Results

  • Patients in the lubiprostone group reported significantly more spontaneous BMs than those in the control group (p = 0.0001) during the first and subsequent weeks.
  • Fifty-seven percent of patients in the lubiprostone group experienced a spontaneous BM within 24 hours of taking the first dose compared to 37% in the placebo group (p = 0.0024).
  • Use of rescue medication was significantly lower in the lubiprostone group ( p = 0.036).
  • Patients in the lubiprostone group reported significant improvement in all related symptoms compared to those in the placebo group (p < 0.05).
  • No significant differences existed between groups in reported events. The most frequent event was nausea. Eight percent of patients in the lubiprostone group were discontinued from the study because of adverse events including nausea, headache, flatulence, and diarrhea.

Conclusions

Taking lubiprostone improved frequency of spontaneous BMs and constipation-related symptoms, with low incidence of treatment-related adverse events.

Limitations

  • Patient diagnoses were not provided, and whether any patients had issues such as opioid-induced constipation is not known.
  • Use of rescue medications was stated to decline, but actual use was not reported and the definition of primary treatment efficacy did not specify spontaneous BM without rescue medication.
  • Applicability to patients with cancer is not clear.

Nursing Implications

Lubiprostone effectively improved constipation in this study; however, applicability to patients with cancer is not clear. Nausea was the most common side effect, which could limit its use in patients with cancer, who may be on other medications and treatments that also cause nausea. Research involving patients with cancer-related constipation should be considered.