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A Randomized Trial for Treatment of Chronic Constipation
Abstract & Commentary
By Malcolm Robinson, MD, FACP, FACG, Emeritus Clinical Professor of Medicine, University of Oklahoma College of Medicine Oklahoma City. Dr. Robinson reports no financial relationship to this field of study.
Synopsis: This study documents the safety and efficacy of oral polyethylene glycol for the long-term treatment of chronic constipation.
Source: DiPalma JA, et al. American Journal of Gastroenterology. 2007;102:1-8
Fifty centers ultimately enrolled 304 evaluable patients with at least a 3-month history of constipation (609 screened). The study was designed to compare the effects of polyethylene glycol vs placebo for the treatment of chronic constipation over a period of 6 months. Chronic constipation was defined (using modified ROME criteria) as less than 3 satisfactory stools per week plus at least one of the following: straining at stool in more than 25% of defecations; lumpy or hard stools in more than 25% of defecations; sensation of incomplete evacuation in more than 25% of defecations. Patients had never taken any form of polyethylene glycol (PEG) for treatment of constipation, and constipation-producing concomitant medications were not allowed at baseline although these might be added if necessary during the course of the study. Other laxative preparations were not allowed except for rescue medication involving 10 mg of oral bisacodyl if severely uncomfortable or if no bowel movement had occurred in the past 4 days. PEG (MiraLAX™) or a matching maltodextrin placebo was given as a powder dissolved in 8 ounces of liquid daily. Treatment success required no use of rescue laxative, satisfactory stools at least 3 times weekly, and one or fewer of the modified ROME criteria outlined above. Data were collected using a telephone-based interactive voice response system. Super efficacy was defined as treatment success with none of the ROME criteria for constipation being present.
Eighty-five percent of study enrollees were female and mean age was 53 years. An average duration of 23 years of constipation was reported by enrollees. Efficacy was demonstrated in 52% of PEG recipients vs 11% with placebo. Active treatment was statistically better than placebo for all of the secondary endpoints (eg, straining, hard stools, incomplete defecation). Super efficacy was achieved in only 9.2% of PEG recipients vs 2.2% with placebo. However, there were no significant differences between groups in the use of rescue bisacodyl tablets during the study. PEG recipients overall (40% vs 25%) were more likely to have treatment-related symptoms such as nausea, loose stools, abdominal distension, and flatulence although none of the individual symptoms reached statistical significance vs the same symptom in the placebo recipients. No laboratory abnormalities were treatment-related in this study; and, in particular, electrolyte balance was not disturbed.
Other authors have also recently published data on the use of tegaserod in chronic constipation that indicate some efficacy. However, DiPalma and colleagues have a pending manuscript for the American Journal of Gastroenterology that found PEG to be superior to tegaserod in efficacy and in tolerability (pending publication this summer). Some years ago, a great many gastroenterologists discovered that regular self-administration of refrigerated liquid PEG-based colon-cleansing solutions could be very helpful in the management of chronic constipation. More recently, companies have developed more conveniently prepared packages of PEG for daily dissolution and consumption (eg, MiraLAX™). Studies like those of DiPalma have demonstrated that there is significant benefit associated with chronic PEG use in longstanding constipation. PEG also appears to be generally safe. However, it is important to note that almost half of the PEG recipients had inadequate clinical responses. Moreover, PEG seemed to cause significantly more GI side effects than placebo. Clearly, we need more and better treatments. This can only occur when constipated patients can be better categorized as to specific underlying pathophysiology, thus allowing treatment to be individualized to address the potentially unique complex of abnormalities in each patient. Clearly, constipated patients with pelvic outlet problems do not need the same treatment as those with colonic inertia, and constipation with irritable bowel syndrome requires yet other therapeutic regimens. For now, there are undoubtedly many patients who will benefit from one or another of the PEG-based regimens for chronic constipation.