Recommendations for pharmacological clinical trials in children with functional constipation: The Rome foundation pediatric subcommittee on clinical trials

Koppen, Ilan J.N.; Saps, Miguel; Lavigne, John V.; Nurko, Samuel; Taminiau, J. A. J. M.; Lorenzo, Carlo Di; Benninga, Marc A.

doi:10.1111/nmo.13294

Cited by 38 publications

(30 citation statements)

References 38 publications

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“…The definitions of functional constipation, pathophysiologic mechanisms, and primary endpoints differ between pediatric and adult studies. 18 Functional constipation is a heterogeneous disorder in children and the underlying pathophysiology is not necessarily limited to abnormal bowel transit. Stool withholding and fear of defecation represent important mechanisms, and it is likely that a drug like lubiprostone may not be able to overcome this problem.…”

Section: Discussionmentioning

confidence: 99%

“…Another factor relates to the outcome measures being used in the present study, because improvement in SBMs as an outcome measure has some inherent problems given the difficulty of capturing BM frequency when children are at school or given that BM frequency is only 1 of the Rome criteria for constipation. 18 Other possibilities include the severity of PFC in children who participated in the study, considering that 72% of children had experienced previous therapy failure. It could be that lubiprostone may be more effective in children with less severe phenotypes, and further studies will be needed to confirm this possibility.…”

Section: Discussionmentioning

confidence: 99%

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Lubiprostone for Pediatric Functional Constipation: Randomized, Controlled, Double-Blind Study With Long-term Extension

Benninga

Hussain

Sood

et al. 2022

Clinical Gastroenterology and Hepatology

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BACKGROUND & AIMS:Pediatric functional constipation (PFC) is a common problem in children that causes distress and presents treatment challenges to health care professionals. We conducted a randomized, placebo-controlled trial (study 1) in patients with PFC (6-17 years of age) to evaluate the efficacy and safety of lubiprostone, followed by an open-label extension for those who completed the placebo-controlled phase (study 2). METHODS:Study 1 (NCT02042183) was a phase 3, multicenter, randomized, double-blind, placebocontrolled, 12-week study evaluating the efficacy and safety of lubiprostone 12 mg twice daily (BID) and 24 mg BID. Study 2 (NCT02138136) was a phase 3, long-term, open-label extension of study 1. In both studies, lubiprostone doses were based on patients' weight. Efficacy was assessed solely based on study 1, with a primary endpoint of overall spontaneous bowel movement (SBM) response (increase of ‡1 SBM/wk vs baseline and ‡3 SBMs/wk for ‡9 weeks, including 3 of the final 4 weeks). RESULTS:606 patients were randomized to treatment (placebo: n [ 202; lubiprostone: n [ 404) in study 1. No statistically significant difference in overall SBM response rate was observed between the lubiprostone and placebo groups (18.5% vs 14.4%; P ¼ .2245). Both the 12-mg BID and 24-mg BID doses of lubiprostone were well tolerated in the double-blind and extension phases, with a safety profile consistent with that seen in adult studies. CONCLUSIONS:Lubiprostone did not demonstrate statistically significant effectiveness over placebo in children and adolescents with PFC but did demonstrate a safety profile similar to that in adults. (Clin-icalTrials.gov: Number: NCT02042183; Number: NCT02138136).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Lubiprostone for Pediatric Functional Constipation: Randomized, Controlled, Double-Blind Study With Long-term Extension

Benninga

Hussain

Sood

et al. 2022

Clinical Gastroenterology and Hepatology

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“…40 To enhance comparison of results between studies, experts recently agreed to use treatment success as a primary outcome in clinical trials, with success simply defined as no longer meeting Rome criteria for FC. 41 Our primary outcome used a stricter definition of success that required no laxative use in the previous 4 weeks.…”

Section: Comparisons With Other Studiesmentioning

confidence: 99%

“…It was therefore unsurprising that observed treatment success rates were lower when using our strict definition. The latest guidelines also recommend using a diary to monitor FC, 41 but we only used a validated self-administered questionnaires to minimize the burden of the study. 28 As a consequence, information about the number of bowel movements, episodes of fecal incontinence, and daily laxative dose may be less accurate.…”

Section: Comparisons With Other Studiesmentioning

confidence: 99%

Physiotherapy for Children with Functional Constipation: A Pragmatic Randomized Controlled Trial in Primary Care

Summeren

Holtman

Kollen

et al. 2020

The Journal of Pediatrics

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Objective: To determine the effectiveness of physiotherapy plus conventional treatment (CT) compared to CT alone for the treatment of functional constipation (FC) in children aged 4-17 years in primary care. Methods: Pragmatic randomized controlled trial with 8 months follow-up. Primary care physicians recruited children diagnosed with FC (n=234), and pediatricians recruited newly referred children with a diagnosis of FC (n=11). CT comprised toilet training, nutritional advice, and laxative prescribing, whereas physiotherapy focused on resolving dyssynergic defecation. The primary outcome was treatment success over 8 months, defined as the absence of FC (Rome III criteria) without laxative use. Secondary outcomes included the absence of FC irrespective of continuation of laxative use and global perceived treatment effect. Results: Children were allocated to CT plus physiotherapy or CT alone (67 per group), mean (SD) age was 7.6 (3.5) years. Results of longitudinal analyses in the intention-to-treat population showed that the treatment success percentage was not statistically improved by adding physiotherapy to CT (aRR 0.80, 95%CI 0.44-1.30). At 4 months, fewer children receiving physiotherapy had treatment success (17%) than children receiving CT alone (28%), but this had equalized by 8 months (42% and 41%, respectively). The percentage of children without FC, irrespective of continuation of laxative use, was not statistically different between groups over 8 months (aRR 1.12, 95%CI 0.82-1.34). Notably, parents reported significantly more global symptom improvement after physiotherapy than after CT (aRR 1.40; 95%CI 1.00-1.73). Conclusions: We find no evidence to recommend physiotherapy for all children with FC in primary care.

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“…This was a single-center retrospective cross-sectional study carried out at the Division of Pediatrics in Tohoku Medical and Pharmaceutical University. Thirty-six patients, who conformed to Rome criteria for FC and visited our center for two years from June 2016, were recruited in the study [2].…”

Section: Subjectsmentioning

confidence: 99%

Utility of Mosapride Citrate in Pediatric Functional Constipation with Low Bowel Movement Frequency

Fujii¹,

Morimoto²

2019

Mathews Journal of Pediatrics

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Functional constipation (FC) in children often requires medical treatment, including pharmacotherapy. Conventional laxatives such as magnesium oxide, sodium picosulfate, lactulose, and carmellose sodium have been used for many years. However, these drugs are often ineffective for patients with intractable FC, requiring continual transanal treatments such as glycerin enemas or bisacodyl suppositories. Mosapride citrate (Mc), a 5-HT4-receptor agonist, is a prokinetic agent that is useful for functional dyspepsia [1]. Symptoms of FD are epigastric discomfort, bloating, appetite loss, pain, or nausea. We administered Mc to pediatric FC patients with the symptoms of functional dyspepsia. This empiric treatment of some patients resulted in significant improvement in bowel movements. In this retrospective study, we assess the effectiveness of Mc combined with the conventional laxatives for FC in a pediatric population. To our knowledge, this

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Recommendations for pharmacological clinical trials in children with functional constipation: The Rome foundation pediatric subcommittee on clinical trials

Cited by 38 publications

References 38 publications

Lubiprostone for Pediatric Functional Constipation: Randomized, Controlled, Double-Blind Study With Long-term Extension

Lubiprostone for Pediatric Functional Constipation: Randomized, Controlled, Double-Blind Study With Long-term Extension

Physiotherapy for Children with Functional Constipation: A Pragmatic Randomized Controlled Trial in Primary Care

Utility of Mosapride Citrate in Pediatric Functional Constipation with Low Bowel Movement Frequency

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