DiPalma, J.A., Cleveland, M.B., McGowan, J., & Herrera, J.L. (2007a). A comparison of polyethylene glycol laxative and placebo for relief of constipation from constipating medications. Southern Medical Journal, 100, 1085–1090.

To compare the safety and efficacy of polyethylene glycol (PEG) 3350 (Miralax^®) versus placebo for treatment of constipation in patients with chronic constipation.

PEG 3350 laxative 17 g or placebo was administered daily for 28 days. Use of nonconstipating medications was allowed, but the use of fiber or other laxatives was not permitted. Patients received a 4 L jug containing Crystal Light^® with or without study medication. The mixture was reconstituted by unblinded study personnel; investigators remained blinded. A daily bowel diary was used to share bowel movement (BM) experiences and answer questions related to study efficacy and safety criteria. Laboratory evaluation was repeated at study conclusion.

• The study reported on a sample of 100 patients (50 in the treatment group and 50 in the placebo group) enrolled and randomized within each site by computer; 93 completed the study.
• Mean patient age was 58 years (range 31 to 84).
• The older subgroup (aged 65 years or older) comprised 28 patients.
• The sample comprised 74 women (74%).
• The sample was 84% Caucasian and 16% African American.
• Mean duration of constipation was 18 years.
• Constipating medications included analgesics, anticholinergics, antidepressants, chemotherapy agents, anticonvulsants, antihistamines, and resins.
• Patients were included in the study if they had constipation as defined by Rome II criteria and were taking medication with a 3% or higher incidence of constipation.
• Patients were excluded if they had an allergy or sensitivity to study medication; had prior gastrointestinal (GI) surgery; had known or suspected GI obstruction, ileus, heart failure, renal failure, ascites, or another known chronic bowel or cardiopulmonary condition; were pregnant or lactating; had loose stool; met criteria for irritable bowel syndrome; and currently were taking or previously had taken PEG.

Four centers in the United States

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

• Relief of Rome II criteria for constipation during the last seven days of treatment period
• Total number of BMs
• Number of patient-reported satisfactory BMs
• Symptoms of gas, cramping, straining at stool, stool consistency, and bloating using a 10-cm visual analog scale

• Patient withdrawal was equivalent for each reason category except lack of efficacy. Three patients withdrew in the placebo group; none withdrew in the treatment group.
• Seventeen patients in the PEG group and 15 patients in the placebo group had analgesics associated with constipating medications. The primary responder for treatment success had a 39% difference in favor of PEG (78% in the PEG group versus 39% in the placebo group, p > 0.001). The older adult subgroup had similar results, but findings were not statistically significant because of the small sample size.
• Baseline constipation (fewer than three BMs per week) was evident in 58% (n = 29) of patients in the PEG group versus 46% (n = 23) of patients in the placebo group.
• Of 609 patients screened, 300 did not meet criteria or failed the 14-day observational period.
• Average BM per week in the final week was 8.1 in the PEG group versus 5.4 in the placebo group (p < 0.001).
• Two of three BMs were rated complete or satisfactory for both treatments.
• Treatment difference for straining and stool consistency was statistically significantly in favor of PEG (p < 0.001).
• No difference existed in gas, bloating, or cramps.

PEG is safe and effective in treating constipation in patients taking constipating medications.

• The study lacked an observational period prior to treatment initiation to confirm constipation status.
• Some patients in the study experienced constipation prior to receiving constipating medication. Medication-induced constipation may respond differently.
• Although the sample included patients with both opioid-induced constipation and chemotherapy-induced constipation, such patients were not included in sufficient numbers to provide dependable data. Additional study is needed.