Effectiveness & Safety of Promelaxin® Microenemas Against Macrogol 4000 P.O. in Chronic Constipation in Children 6-48 Months

Study Overview
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Brief Summary
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The study is aimed at the efficacy and safety evalutation of the study treatments through a 2-weeks study period and the subsequent follow-up-

Detailed Description
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This multicenter, prospective, randomized, controlled trial will be conducted on 120 infants-children with a diagnosis of chronic functional constipation according to the definition of Criteria of Rome III. The enrolled subjects will be randomized according to an electronically generated randomization list in 2 groups: one group will receive micro-enemas of Promelaxin® (Group A) while the second group will receive Macrogol 4000 per os (Group B) . Children will receive the dedicated treatment for two weeks and then undergo a follow-up period of a maximun of 6 weeks. The hypothesis is that the protective micro-enema will help achieving regular evacuation by its local antinflammatory non-pharmacological action. This hypothesis is based on the finding that local anal inflammation can cause functional constipation due to discomfort and pain during evacuation or by influencing reflexes.

Official Title
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Multicenter, Prospective, Comparative, Randomized Controlled Clinical Trial to Evaluate the Performance and the Safety of Promelaxin® Micro-enemas Vs. Macrogol 4000 Per os in the Treatment of Functional Chronic Constipation in Children Aged Between 6 and 48 Months.

Conditions
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Chronic Functional Constipation

Intervention / Treatment
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* Device: micro-enema with Promelaxin
* Drug: Macrogol 4000


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic functional constipation according to Rome III criteria No stool softeners therapy administered during the 7 days prior to Baseline Visit Signature of informed consent from by both parents or legal representative Willingness to follow the study schedule Exclusion Criteria: Suspicious or established diagnosis of organic constipation Delayed emission of meconium in the term newborn Presence of severe inflammatory bowel disease (such as ulcerative colitis, Crohn's disease), toxic megacolon Presence/Risk of gastroinstestinal perforation Presence/Suspiceous intestinal obstruction of symptomatic stenosis (Undeterminated) Abdominal pain Hypersensitivity to macrogol (polyethylene glycol) or to one or more product excipients Hereditary fructose intolerance Known hypersensitivity or allergy to any Promelaxin component Presence of any other medical condition that contraindicate the use of Promelaxin® or Macrogol 4000

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 48 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized between two treatment arms
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: micro-enema with Promelaxin<br>2,5 g, 5 g or 2X5 g (calculated considering patient age) have to be administered daily (in the evening) for one week, once every other day for the second week and as needed for the following 6 weeks | Device: micro-enema with Promelaxin<br>* The intervention has a lubricating, protective action on the anus and rectum and a balanced osmotic action which elicits the evacuation reflex.<br>* Other names: Melilax;|
| Active Comparator: Macrogol 4000<br>One/Two sachets of the study treatment has to be solubilized in 50mL of water and then administered daily. The administration should take place in the morning (the first sachet or in the event that only one sachet/day should be administered) and in the evening (second sachet). | Drug: Macrogol 4000<br>* Stool softener<br>* Other names: Paxabel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of constipation evaluated as a reduction of the typical symptoms of chronic functional constipation | Treatment should be considered as successful if the child will show, at Visit 3, 3 or more defecations per week associated with an increase of 1 or more defecations versus baseline. | day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| score of the parents quality of life calculated on day 21 and 56 | parents quality of life questionnaire | day 21 and day 56 | 
| score of the children quality of life calculated on day 21 and 56 | children quality of life questionnaire | day 21 and day 56 | 
| Gastrointestinal symptoms in children on days 14, 21 and 56 | gastrointestinal symptoms recording through/following treatment | day 14, day 21 and day 56 | 
| changes in the intestinal microbioma on day 21 and 56 | the intestinal microbioma will be analysed in laboratory to see whether a treatment influence can be measured | day 21 and day 56 | 
| Evaluation of the normalization of intestinal activity measured by recording frequency of evacuations and stool consistency on day 14, 21 and 56 |  | day 14, day 21 and day 56 | 
| Product Safety | Adverse events reported by parents/legal representative of the subject | day 14, day 21 and day 56 | 
| Change in stool consistency | Reduction of stool consistency with increase of 1 or more points on Bristol Stool Form Scale or Amsterdam scale | day 14, day 21 and day 56 |