Promelaxin Microenemas Are Non-inferior to Oral Polyethylene Glycol for the Treatment of Functional Constipation in Young Children: A Randomized Clinical Trial

Abstract

Background: Polyethylene glycol (PEG) is recommended as first-line treatment of pediatric functional constipation. However, the oral route of administration is often poorly feasible in children mostly due to poor palatability. Promelaxin microenemas exert a topical evacuative action and may offer a valuable option in pediatric FC.Aim: To assess whether Promelaxin microenemas would be non-inferior to PEG 4000 in young children with FC.Methods: This is a randomized, open-label, multi-centric, non-inferiority trial enrolling infants and young children aged 6–48 months, with FC according to Rome III criteria. After 1 week of run in, children were randomized to 2 weeks of Promelaxin or PEG, followed by a 6-week on-demand treatment period. Primary endpoint was response rate to randomized treatment, with “response” defined as at least 3 evacuations per week and an average increase of at least one evacuation per week as compared to baseline. Safety, stool consistency and the analysis of fecal microbiota were secondary endpoints.Results: Out of the 158 patients who entered the trial, 153 patients were treated (77 and 76, PEG and Promelaxin arm, respectively). In the primary analysis, the 95% confidence interval (CI) for the treatment's effect lay entirely above the non-inferiority margin in both Full Set (FAS) and Per Protocol (PP) analyses, providing evidence of the non-inferiority of Promelaxin vs. PEG 4000 [response rate difference: 16.5% (CI 1.55–31.49%) and 11.03% (CI −5.58 to 27.64%), FAS and PP analyses, respectively]. Mean compliance to the randomized treatment was >80% in both arms. Secondary endpoints did not significantly differ between the two arms, except for the average number of total days of on-demand treatment that was significantly lower in the Promelaxin arm [14.6 (12.7) vs. 9.8 (9.1), mean (SD); primary endpoint responders in PEG and Promelaxin arm, respectively; p = 0.027]. Microbiota evenness significantly increased in the PEG 4000 arm at V4 as compared to the Promelaxin arm (p < 0.05). In addition, at V5, patients treated with PEG showed a significantly decreased microbiota density as compared to patients treated with Promelaxin (p = 0.036).Conclusions: Promelaxin microenemas are non-inferior to oral PEG in children with FC.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT02751411.

Substance-based medical devices made of natural substances: An opportunity for therapeutic innovation

“…1-In improving the benefit/risk ratio of current therapeutics, with a aim of minimal impact on the physiology of the whole body, especially in the long term, and on the environment. 2-In managing the complexity of new diseases and treatments: degenerative, metabolic and functional diseases, as well as multifactorial syndromes, occur at an increasingly higher frequency as the population ages (Van den Berg et al, 2006, Kelishadi 2007, Cockerham et al, 2017, GBD 2015Obesity Collaborators 2017, DeBoer 2019, Cobiac and Scarborough 2021, Dellafiore et al, 2022, Guarino et al, 2022, Nguyen et al, 2022) and often have unsatisfactory or inadequate treatments (Black and Ford, 2021;Strisciuglio et al, 2021;Bousaba et al, 2022;Negi et al, 2022;Singh et al, 2022).…”

Gastrointestinal functional disorders can benefit from the use of medical devices made of substances

“…Particularly those with FC, both children and adults, have been the object of multiple studies and various meta-analyses, as shown in Table 3. (Strisciuglio et al, 2021) conducted a randomized noninferiority trial in order to assess whether microenemas of Promelaxin (A complex of honeys + Aloe and Mallow polysaccharides) are not inferior to oral polyethylene glycol (PEG) 4,000 as topical therapy in children with FC according to Rome III criteria (Longstreth et al, 2006). They enrolled infants and young children aged 6-48 months who were randomized to 2 weeks of Promelaxin microenemas or PEG daily, followed by a 6-week ondemand treatment period.…”

New regulation on medical devices made of substances: Opportunities and challenges for pharmacological and toxicological research

“…Several chronic, multifactorial disorders with unsatisfying medical treatment can benefit from MDMS regulation; this is the case of treatment of some gastrointestinal illness (Corazziari, 2020;Bilia et al, 2021) or metabolic disorders (Guarino et al, 2021), even in the pediatric population (Strisciuglio et al, 2021;Stagi, 2022). In this scenario, MDR provides opportunities for therapeutic innovation with complex substances while guaranteeing patients with standards of efficacy and safety.…”