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Polyethylene glycol 3350 plus electrolytes for pediatric chronic constipation: An open-label clinical study in Japan.
Gondo, M, Nagata, S, Shinbo, K, Oota, A, Tomomasa, T
Pediatrics international : official journal of the Japan Pediatric Society. 2020;(5):600-608
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BACKGROUND Despite the abundance of study evidence for its efficacy and tolerability for the treatment of constipation in other countries, polyethylene glycol 3350 plus electrolytes (PEG3350+E) was not available in Japan until recently. The purpose of this study was to establish the efficacy and safety of PEG3350+E for the treatment of functional constipation in children in Japan. METHODS Japanese children aged 2-14 years with a mean spontaneous bowel movement (SBM) frequency of 2 times/week or less for at least 2 months prior to informed consent were enrolled into the study. After a 2-week screening period, treatment with PEG3350+E was initiated on the day of enrollment and continued for 12 weeks. Change in SBM frequency from screening period week 2 (baseline) to treatment period week 2 was set as the primary endpoint. Secondary endpoints and adverse events were also examined. RESULTS Thirty-nine patients were enrolled and completed the 12-week study period. The SBM frequency (mean ± SD) at baseline and treatment period week 2 was 1.00 ± 0.89 and 6.54 ± 4.38, respectively. The change in SBM frequency was 5.54 ± 4.55 (one-sample t test, P < 0.0001) and remained stable through week 12. Stool consistency was also improved over the entire treatment period. Three mild adverse drug reactions were reported: decreased appetite, abdominal pain, and diarrhea (each in 1 of 39 [2.6%] patients). CONCLUSION PEG3350+E can be considered as a new treatment option for chronic constipation in children in Japan. CLINICAL TRIAL REGISTRATION NUMBER Japic CTI-163167.
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PEG 3350 Versus Lactulose for Treatment of Functional Constipation in Children: Randomized Study.
Jarzebicka, D, Sieczkowska-Golub, J, Kierkus, J, Czubkowski, P, Kowalczuk-Kryston, M, Pelc, M, Lebensztejn, D, Korczowski, B, Socha, P, Oracz, G
Journal of pediatric gastroenterology and nutrition. 2019;(3):318-324
Abstract
OBJECTIVES The aim of this study was to compare the clinical efficacy and tolerance of polyethylene glycol 3350 (PEG) and lactulose for the treatment of functional constipation in infants and children. METHODS This randomized, multicenter study covered 12 weeks of treatment and 4 weeks of follow-up of patients with functional constipation. Patients were randomized (central randomization) to receive either PEG or lactulose. The primary end points were the number of defecations per week after 12 weeks of treatment and improvement in stool consistency of at least 2 points in the Bristol scale. The secondary end point was the presence of adverse events. Bowel movements ≥3 per week and stool consistency ≥2 (Bristol scale) were considered as successful treatment. RESULTS We enrolled 102 patients (M 57, F 45) aged 3.62 ± 1.42 years and 88 completed the study. At week 12, good clinical outcome was achieved in 98% (PEG) and 90% (lactulose). The PEG group had more defecations per week compared with the lactulose group (7.9 ± 0.6 vs 5.7 ± 0.5, P = 0.008) and both groups had similar frequency of defecation with pain (5% vs 5%, P = 0.9), stool retention (7% vs 10%, P = 057), large volume of stools (30% vs 31%, P = 0.9) and hard stools (7% vs 13%, P = 0.58). There were more patients with side effects in the lactulose group (15 vs 23, P = 0.02), mostly bloating and abdominal pain. CONCLUSIONS PEG 3350 is more effective and causes fewer side effects than lactulose in the treatment of constipation in infants and children.
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Polyethylene glycol 3350 plus electrolytes for chronic constipation: a 2-week, randomized, double-blind, placebo-controlled study with a 52-week open-label extension.
Nakajima, A, Shinbo, K, Oota, A, Kinoshita, Y
Journal of gastroenterology. 2019;(9):792-803
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BACKGROUND Although polyethylene glycol 3350 plus electrolytes (PEG3350 + E) is the most widely used osmotic laxative in Europe, prospective data on its long-term (over 6 months) safety and efficacy are not available to date. METHODS Japanese patients with chronic constipation were randomized to receive PEG3350 + E or placebo for 2 weeks orally. Following this, the patients received PEG3350 + E in the 52-week extension study. The starting dose was 13.7 g/day dissolved in 125 mL of water, and dose titration was allowed (upper limit 41.1 g/day) according to the patient's bowel condition. The primary efficacy endpoint was the change from baseline in frequency of spontaneous bowel movements (SBMs) at week 2 in the double-blind study. Secondary endpoints and adverse events were assessed. Safety and efficacy were also assessed in the extension study. RESULTS Among 204 patients who provided informed consent, 156 were randomized and included in the full analysis. The frequency of SBMs was significantly higher with PEG3350 + E [least squares mean (LSM) 4.3, 95% confidence interval (CI) 3.6-4.9] compared with placebo (LSM 1.6, 95% CI 1.2-2.1; P < 0.0001). A total of 153 patients entered the extension study; PEG3350 + E led to a sustained improvement in bowel function. The common adverse drug reactions during the entire study period were mild gastrointestinal disorders (abdominal pain 4.5%, diarrhea 3.8%, nausea 3.2%, abdominal distension 2.6%). CONCLUSIONS Treatment with PEG3350 + E resolved constipation in the short term, was well tolerated, and led to sustained improvement in bowel function in the long-term treatment of Japanese patients with chronic constipation. CLINICAL TRIAL REGISTRATION NUMBER Japic CTI-163167.
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The effectiveness of Lactobacillus reuteri DSM 17938 as an adjunct to macrogol in the treatment of functional constipation in children. A randomized, double-blind, placebo-controlled, multicentre trial.
Wegner, A, Banaszkiewicz, A, Kierkus, J, Landowski, P, Korlatowicz-Bilar, A, Wiecek, S, Kwiecien, J, Gawronska, A, Dembinski, L, Czaja-Bulsa, G, et al
Clinics and research in hepatology and gastroenterology. 2018;(5):494-500
Abstract
OBJECTIVE Constipation is one of the most common problems among children, with a prevalence ranging from 7 to 30%. It is treated with defecation training and laxative medications. However, many patients do not respond to the standard therapy. There is, therefore, an increasing interest in probiotics for the treatment of functional constipation. STUDY DESIGN The aim of this study was to assess the effectiveness of Lactobacillus reuteri DSM 17938 as an adjunct to macrogol in the treatment of functional, intractable constipation in children. A double-blind, placebo-controlled, randomized, multicentre trial involved a group of 129 children with functional constipation who were treated with a poor effect for at least two months prior to the study. Patients were randomly assigned to one of the two groups: 1. L. reuteri DSM 17938 and macrogol or 2. macrogol and matching placebo for 8 weeks. RESULTS 121 patients completed the study. Almost all patients (119/129) increased their bowel movements in both groups (59 vs 60, ns.) and there was no statistically significant difference in the number of bowel movements per week in week 8 between the study and the placebo group (7.5±3.3 vs 6.9±2.5, respectively). Additionally, there were no significant differences between groups in the numbers of patients complaining of pain during defecation (13/47 vs 8/53), abdominal pain (19/41 vs 25/36), withholding stools (15/45 vs 13/48), passing hard stools (7/53 vs 3/58) or large stools (14/46 vs 12/49), and faecal incontinence (17/43 vs 11/50). CONCLUSION L. reuteri DSM 17938 supplementation as an additional therapy to macrogol did not have any beneficial effect on the treatment of functional constipation in children aged 3-7 years.
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[Efficacy, tolerance and safety of polyethylene glycol 3350 plus electrolytes for the treatment of functional constipation in children].
Infante Pina, D, Segarra Cantón, O, Vilalta Casas, R, Carnicer de la Pardina, J, López Liñán, MJ, Molera Busoms, C
Anales de pediatria (Barcelona, Spain : 2003). 2014;(5):278-84
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OBJECTIVE To assess the renal safety of treatment with polyethylene glycol 3350 with electrolytes at 1, 3 and 6 months, its gastrointestinal tolerance and dose effectiveness. PATIENTS AND METHODS Three groups of 30 healthy patient aged 2-10 years (mean 6.2 years) who suffered functional constipation (Rome III criteria) with 1, 3 and 6 months of treatment were evaluated. Efficacy was evaluated by the change in the number of stools per week and stool consistency (Bristol scale). Urine screens, sodium and osmolality, were performed at the beginning and after 1, 3 and 6 months of treatment. Stool sample NIRA (near-infrared reflectance analysis) and hydrogen breath test analysis samples were performed on the one-month treatment group. RESULTS The mean dose was 0.37g/kg/day (range 0.18 to 0.8) titrated according to age, weight and response. The number of stools per week during treatment (2.4±0.64) showed a significant difference (P<.001) vs (6.21±1.5) after treatment. There was also a significant difference in the Bristol scale score (1.9±0.75 vs 4.9±1.1 [P<.001]). The mean sodium intake was 112mg (5mg/kg/day [range 4-12mg/kg/day]). The values of sodium and urine osmolality were normal in all groups with no statistical difference compared to normal control values (90 healthy children without treatment). NIRA values were normal in all patients. The hydrogen breath test was normal with a median of 7ppm. CONCLUSION There were no adverse renal biochemical parameters or gastrointestinal disorders. Tolerance and efficacy was shown to be optimal. Polyethylene glycol 3350 with electrolytes can be safely recommended for the treatment of functional constipation in children in the short and long term.
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Prucalopride is no more effective than placebo for children with functional constipation.
Mugie, SM, Korczowski, B, Bodi, P, Green, A, Kerstens, R, Ausma, J, Ruth, M, Levine, A, Benninga, MA
Gastroenterology. 2014;(6):1285-95.e1
Abstract
BACKGROUND & AIMS Prucalopride is a selective, high-affinity agonist of the 5-hydroxytryptamine (serotonin) receptor 4 that enhances motility in the gastrointestinal tract. We performed a multicenter, randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of prucalopride in children (6 months to 18 years old) with functional constipation. METHODS Children with functional constipation, based on the Rome III criteria, were given prucalopride (children ≤ 50 kg were given a 0.04 mg/kg oral solution; children >50 kg were given a 2-mg tablet) or placebo once daily for 8 weeks. The primary efficacy end point was the proportion of children with toileting skills who had a mean of ≥ 3 spontaneous bowel movements/week and ≤ 1 episode of fecal incontinence/2 weeks, from study weeks 5-8 (responders). Adverse events, clinical laboratory values, and electrocardiograms were monitored. RESULTS Efficacy and safety were assessed in 213 children (106 prucalopride, 107 placebo). Twenty-five percent were younger than 4 years old, 50% were 4-11 years old, and 25% were 12-18 years old; 55.4% were girls. At screening, 62.3% of patients in the prucalopride group and 55.1% in the placebo group had a history of fecal incontinence; 60.4% and 55.1% in the prucalopride and placebo groups, respectively, had a mean of ≤ 1 spontaneous bowel movements/week. The proportion of responders was similar between groups (prucalopride, 17.0% and placebo, 17.8%). There were no statistically significant differences in the primary efficacy end point when patients were stratified by sex, age group, or country. The incidence of treatment-emergent adverse events was similar in the prucalopride (69.8%) and placebo (60.7%) groups. CONCLUSIONS Prucalopride, although generally well tolerated, was not more effective than placebo in children with functional constipation. ClinicalTrials.gov Number: NCT01330381.
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Randomised clinical trial: the safety and efficacy of AST-120 in non-constipating irritable bowel syndrome - a double-blind, placebo-controlled study.
Tack, JF, Miner, PB, Fischer, L, Harris, MS
Alimentary pharmacology & therapeutics. 2011;(8):868-77
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BACKGROUND There is a need for safe and effective treatment options for irritable bowel syndrome (IBS). AST-120 (spherical carbon adsorbent) is a non-absorbed, carbon-based adsorbent with extensive adsorbing capability for histamine, serotonin and other substances implicated in IBS pathogenesis. AIM: To evaluate the efficacy and safety of AST-120 in non-constipating forms of IBS. METHODS This randomised, double-blind, placebo-controlled trial conducted in the US and Belgium enrolled 115 male and female patients fulfilling Rome III criteria for IBS; individuals with predominantly constipation symptoms were excluded. Subjects were randomised to AST-120 2 g tds or placebo for an 8-week double-blind treatment period, followed by a 2-week single-blind placebo washout and 8-week single-blind active treatment. The primary efficacy endpoint was the proportion of subjects achieving at least a 50% reduction in the number of days with abdominal pain compared with baseline. RESULTS At Week 4, 26.8% of subjects treated with AST-120 responded on the primary endpoint vs. 10.2% in the placebo arm (P=0.029); at Week 8 response rates were 32.1 and 25.4% respectively (NS). More AST-120 treated subjects experienced improvement in bloating and stool consistency. These benefits abated when AST-120 was replaced by placebo, and resumed once AST-120 was restarted. The frequency of adverse events with AST-120 were less than or equal to placebo. CONCLUSIONS AST-120 is safe and well-tolerated and reduces pain and bloating in non-constipating IBS, although beneficial effects may be limited in duration. AST-120 represents a locally acting, non-absorbed, novel treatment for IBS and warrants further studies.
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A randomized placebo-controlled phase IIb trial of a3309, a bile acid transporter inhibitor, for chronic idiopathic constipation.
Chey, WD, Camilleri, M, Chang, L, Rikner, L, Graffner, H
The American journal of gastroenterology. 2011;(10):1803-12
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OBJECTIVES A3309 is a minimally absorbed ileal bile acid (BA) transporter (IBAT) inhibitor. We conducted an 8-week, multicenter, randomized, double-blind, placebo-controlled, parallel group, phase IIb study, which evaluated A3309 in patients with chronic idiopathic constipation (CIC). METHODS Patients with CIC (modified Rome III criteria and <3 complete (CSBM) spontaneous bowel movements (SBMs)/week during the 2-week baseline) were randomized to 5, 10, or 15 mg A3309 or placebo once daily. The primary end point was change in SBM number during week 1 compared with baseline. Other bowel and abdominal symptoms were assessed as secondary end points. Serum 7αC4 and lipids were evaluated as biomarkers of BA synthesis/loss. RESULTS In all, 190 patients (mean 48 years, 90% female) were randomized. Mean increase (95% confidence interval) in SBM for week 1 were 1.7 (0.7-2.8) for placebo vs. 2.5 (1.5-3.5), 4.0 (2.9-5.0), and 5.4 (4.4-6.4) for 5 mg, 10 mg (P<0.002), and 15 mg (P<0.001) A3309, respectively. Increased stool frequency was maintained over 8 weeks. Time to first SBM and CSBM were significantly reduced in the 10- and 15-mg A3309 groups compared with placebo. Straining and bloating decreased with A3309 compared with placebo (P<0.05). Increased 7αC4 and reduced low-density lipoprotein cholesterol with A3309 suggested increased BA synthesis and BA loss. The most common adverse events (AEs) were abdominal pain and diarrhea, which occurred most commonly in the 15-mg A3309 group. No drug-related serious AEs were observed. CONCLUSIONS A3309 increased stool frequency and improved constipation-related symptoms in CIC; effects were maintained over 8 weeks of treatment.
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Treatment of functional constipation with the Yun-chang capsule: a double-blind, randomized, placebo-controlled, dose-escalation trial.
Jia, G, Meng, MB, Huang, ZW, Qing, X, Lei, W, Yang, XN, Liu, SS, Diao, JC, Hu, SY, Lin, BH, et al
Journal of gastroenterology and hepatology. 2010;(3):487-93
Abstract
BACKGROUND AND AIM Functional constipation is a common functional bowel disorder for which there is no reliable medical treatment. This study was designed to determine the therapeutic efficacy and safety of the Yun-chang capsule, a Chinese herbal formula, in the treatment of patients with functional constipation. METHODS In our multi-center, prospective, double-blind, randomized, placebo-controlled, dose-escalation trial, patients with functional constipation received 70 mg of Yun-chang capsule plus 35 mg placebo (group A), 105 mg of Yun-chang capsule (group B), or 105 mg placebo (group C), three times daily for 2 weeks. The primary end-points were the changes in main symptom score and cumulative symptom score 2 weeks after the treatment. The secondary end-points were adverse events. RESULTS A total of 140 patients were recruited and 132 met the inclusion criteria; 44 patients constituted each of the three treatment groups. Compared with patients in group C, patients in groups A and B had significant improvement in the main symptom score, cumulative symptom score, the change from baseline of the main symptom score, and the change from baseline of the cumulative symptom score at week 1 and week 2. The scores showed slight superiority of group B over group A at week 1 and week 2, although these differences were not statistically significant. There were no differences in adverse events. CONCLUSIONS The Yun-chang capsule is efficacious and safe for the treatment of patients with functional constipation. Larger and longer-term trials are required to fully assess the benefits and safety of this treatment for functional constipation.
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Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of sodium picosulfate in patients with chronic constipation.
Mueller-Lissner, S, Kamm, MA, Wald, A, Hinkel, U, Koehler, U, Richter, E, Bubeck, J
The American journal of gastroenterology. 2010;(4):897-903
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OBJECTIVES Although it has been used as a laxative for many years, high-quality trials assessing the efficacy of the laxative sodium picosulfate (SPS) are lacking. The purpose of this study was to assess the efficacy and safety of 4-week treatment with SPS in patients with functional constipation as defined by the Rome III diagnostic criteria. METHODS This study was a randomized, double-blind, placebo-controlled, parallel-group study in 45 general practices in Germany. A total of 468 patients with chronic constipation presenting to their general practitioner and fulfilling the Rome III diagnostic criteria were screened. After a 2-week baseline period, 367 patients were randomized to either SPS drops or matching placebo in a 2:1 ratio for 4 weeks. Dose titration was permitted throughout treatment. Patients without a bowel movement for more than 72 h were allowed to use a "rescue" bisacodyl suppository. The primary end point was the mean number of complete spontaneous bowel movements (CSBMs) per week. A spontaneous bowel movement (SBM) was defined as a stool not induced by rescue medication, whereas a CSBM was defined as an SBM associated with a sensation of complete evacuation. RESULTS The mean number (+/-s.e.) of CSBMs per week increased from 0.9+/-0.1 to 3.4+/-0.2 in the SPS group and from 1.1+/-0.1 to 1.7+/-0.1 in the placebo group (P<0.0001). The percentage of patients reaching an increase of > or =1 in the mean number of CSBMs per week compared to baseline was 65.5% vs. 32.3%, respectively (P<0.0001). The percentage of patients reaching a mean number of at least three CSBMs per week was 51.1% in the SPS group and 18.0% in the placebo group (P<0.0001). After 24 h, approximately 69% of patients in the SPS group and 53% in the placebo group had their first SBM. The SPS dose was titrated down during the study by nearly 50% of patients. Assessment of quality of life (QoL) by the constipation-related Patient Assessment of Constipation (PAC)-QoL questionnaire showed significant improvement in SPS-treated patients compared to the placebo group. CONCLUSIONS Treatment of chronic constipation with SPS improves bowel function, symptoms, and QoL and is well tolerated. The dose can be adjusted individually while maintaining benefit.