Robust Clinical Evidence
Robust Clinical Evidence
Start with MiraLAX®, proven effective in multiple clinical trials1-5
MiraLAX® Grade A recommendation, Level I evidence, is a higher rating than fibers or stool softeners
Watch Dr. Satish Rao (lead author of the review) present highlights of the findings
PEG = polyethylene glycol.
*A systematic review across PubMed and Embase of randomized controlled trials (≥4-week duration) that evaluated OTC constipation preparations between 2004 and 2020. Studies meeting the following selection criteria were included: 1) randomized controlled trial (placebo or active comparator); 2) parallel or crossover design; 3) established definition of constipation (preferably ROME criteria); 4) minimum duration of 4 weeks of active treatment; 5) well-defined clinical endpoints. Studies were scored using US Preventive Services Task Force criteria (0-5 scale) including randomization, blinding, and withdrawals. The strengths of evidence were adjudicated within each therapeutic category, and recommendations were graded (A, B, C, D, or I) based on level of evidence (Level I, good; Level II, fair; or III, poor).
In another clinical study, patients taking MiraLAX® reported relief in half the time of that reported by those who waited.6
Summary of key MiraLAX® clinical studies and analyses
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Statistically significant improvement in primary endpoint
- Similar efficacy was seen in a subgroup of 75 elderly subjects
Statistically significant improvement in secondary endpoints
- There were no clinically significant changes in electrolytes or hematology measures
- There were no statistically significant differences in treatment emergent effects except for gastrointestinal events such as diarrhea, flatulence, and nausea
- These events occurred more frequently in subjects taking MiraLAX® (40% vs 25%, P=0.015)
- However, when considered individually, these events were not statistically significant compared with placebo
aPatients with modified Rome functional constipation criteria of <3 satisfactory bowel movements per week, with straining in >25% of defecations, hard or lumpy stools in >25% of defecations, or sensation of incomplete evacuation in >25% of defecations for a 3-month period were randomized to treatment with 17 g PEG 3350 (n=204) daily or placebo (n=100).2
bTreatment success was defined as no rescue laxative use, ≥3 satisfactory stools per week, and ≤1 remaining symptom of the modified Rome criteria defined above.2
- The safety and effectiveness of MiraLAX® were evaluated in people with constipation
- Twenty-three patients with constipation were given the normal daily dose (17 g) of MiraLAX® or a placebo, after which they recorded each bowel movement and associated symptoms in a diary and watched for any changes in frequency
- After 14 days, patients given MiraLAX® had significantly more bowel movements than those on placebo (7.0 vs 3.6, respectively, in week 2; P<0.001), and they had no serious side effects
- Patients taking constipation-inducing medications (≥3% incidence of constipation) were randomized to treatment with 17 g PEG 3350 (n=50) daily or placebo (n=50) for 28 days
- The primary efficacy variable of treatment success was based on the presence of no more than one of the following in 25% of bowel movements or <3 bowel movements per week over the last 7 days of treatment:
- Straining
- Lumpy/hard stool
- Incomplete evacuation
- Anorectal obstruction
- Manual maneuvers - PEG 3350 was significantly superior vs placebo in the primary efficacy endpoint of treatment success: 78.3% vs 39.1% (P<0.001), respectively
- Statistically significant differences in favor of PEG 3350 over placebo were observed:
- After first week of treatment:
- Total number of bowel movements per week
- Number of complete bowel movements
- Number of satisfactory bowel movements
- For all treatment weeks:
- Straining
- Stool consistency
- There were no statistically significant treatment-emergent adverse events, including GI complaints
Statistically significant improvement in primary endpoint
Statistically significant improvement in secondary endpoints
- Treatment differences for straining at stool and stool consistency statistically significantly favored MiraLAX® for all treatment weeks, P<0.001
- There were no significant differences in treatment emergent effects between study groups
aA randomized, 28-day, double-blind, placebo-controlled, parallel-group study that enrolled patients from 4 US centers who had chronic constipation and were taking medications associated with symptoms of constipation.4
bMedications causing constipation included analgesics, antihypertensives, anticholinergics, antidepressants, chemotherapeutic agents, anticonvulsants, antihistamines, and resins.4
cThe primary efficacy endpoint of “Treatment Success” was based on assessment of ROME II criteria during the last 7 days of treatment for each patient. Treatment success (response) was defined as meeting no more than one of the following ROME II criteria during the 7-day period before the end of treatment: straining 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; sensation of anorectal obstruction/blockage in more than 25% of defecations; manual maneuvers to facilitate >25% of defecations; <3 bowel movements per week.4
- A 2011 Cochrane review identified and reviewed all randomized controlled trials comparing the use of lactulose and polyethylene glycol in the management of fecal impaction and chronic constipation (Rome III criteria) in adults and children. Both monotherapy and crossover studies were reviewed
- The findings of this meta-analysis indicate that polyethylene glycol is better than lactulose in outcomes of stool frequency per week, form of stool, relief of abdominal pain, and the need for additional products
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References: 1. Rao SSC, Brenner DM. Efficacy and safety of over-the-counter therapies for chronic constipation: an updated systematic review. Am J Gastroenterol. 2021;116(6):1156-1181. doi:10.14309/ajg.0000000000001222 2. DiPalma JA, Cleveland MvB, McGowan J, Herrera JL. A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation. Am J Gastroenterol. 2007;102:1436-1441. doi:10.1111/j.1572-0241.2007.01199.x 3. Cleveland MvB, Flavin DP, Ruben RA, Epstein RM, Clark GE. New polyethylene glycol laxative for treatment of constipation in adults: a randomized, double-blind, placebo-controlled study. South Med J. 2001;94(5):478-481. 4. DiPalma JA, Cleveland MB, McGowan J, Herrera JL. A comparison of polyethylene glycol laxative and placebo for relief of constipation from constipating medications. South Med J. 2007;100(11):1085-1090. doi:10.1097/SMJ.0b013e318157ec8f 5. Lee-Robichaud H, Thomas K, Morgan J, Nelson RL. Lactulose versus polyethylene glycol for chronic constipation. Cochrane Database Syst Rev. 2010;(7):CD007570. doi:10.1002/14651858.CD007570.pub2 6. Data on file, Bayer Healthcare. 7. DiPalma JA, DeRidder PH, Orlando RC, Kolts BE, Cleveland MvB. A randomized, placebo-controlled, multicenter study of the safety and efficacy of a new polyethylene glycol laxative. Am J Gastroenterol. 2000;95(2):446-450. doi:10.1111/j.1572-0241.2000.01765.x
Start with MiraLAX®: A first-line OTC laxative recommendation across constipation clinical guidelines
Constipation management guidelines from multiple professional organizations recommend PEG, the active ingredient in MiraLAX®, as a first-line treatment1-3
- Guidelines either don’t mention stool softeners like docusate or don’t recommend them prominently
Recommendations
AAFP=American Academy of Family Physicians; ACG=American College of Gastroenterology; AGA=American Gastroenterological Association; ASCRS=American Society of Colon and Rectal Surgeons; Rome IV 2016=the Rome Foundation’s 2016 publication in Gasteroenterology.
*Consistent, good-quality, patient-oriented evidence.
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References: 1. Paquette IM, Varma M, Ternent C, et al. The American Society of Colon and Rectal Surgeons’ Clinical Practice Guidelines for the Evaluation and Management of Constipation. Dis Colon Rectum. 2016;59(6):479-492. doi:10.1097/DCR.0000000000000599 2. Bharucha AE, Dorn SD, Lembo A, Pressman A. American Gastroenterological Association medical position statement on constipation. Gastroenterology. 2013;144(1):211-217. doi:10.1053/j.gastro.2012.10.029 3. Ford AC, Moayyedi P, Lacy BE, et al. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gasteroenterol. 2014;109(Suppl 1):S2-S26. 4. Lacy BE, Mearin F, Chang L, et al. Bowel disorders. Gastroenterology. 2016;150(6):1393-1407. doi:10.1053/j.gastro.2016.02.031 5. Mounsey A, Raleigh M, Wilson A. Management of constipation in older adults. Am Fam Physician. 2015;92(6):500-504.
