Prospective Interventional Study to Evaluate the Effect of a Medical Device Made of Substances in Reducing Signs and Symptoms in Patients with Hemorrhoidal Disease

Background and Aim: Hemorrhoidal Disease (HD) is a chronic pathology and is fairly common in the general population. For this reason, conservative therapies need to be at the same time effective and tolerated. The topical medications available usually contain either a combination of local anesthetics with anti‐inflammatories or muscle relaxants, thus addressing a single mechanism, if any, of those that underlie symptoms onset. As a consequence, evidence of efficacy of these drugs is currently limited and the needed tolerability and safety from a topical treatment of HD is not always evident. The aim of the present study was to evaluate efficacy and tolerability of a 100% natural ointment, a medical device made of substances, for the symptomatic treatment of HD. Methods: Symptomatic grade I or II HD patients with 0-100 VAS score for HD-related discomfort ≥ 30 were treated for 10 days. Outcome measures included variation of HD subjective symptoms (discomfort, pain, itching and burning) and objective signs (bleeding and anal leakage) at day 3, 7 and 10, and the presence of prolapse after treatment. Statistical analysis: for the analysis of the primary endpoint (i.e. reduction of discomfort), missing data in the full analysis set (FAS) population were replaced using the “Last Observation Carried Forward” (LOCF) method. For the analyses of secondary endpoints, Poisson mixed model was used to evaluate symptom variation (VAS). Bleeding and anal leakage were recoded as negative or positive in two different variables (grade 1 and 2) derived from their frequency (i.e., for grade1, each of the clinical signs was considered Negative if the patient reported frequency was “Never”; recoded as Positive if any other frequency category was reported) and frequencies of positive patients in each grade were compared by Logistic Mixed model. Mixed models were used to take in account repeated data for the same subject. Missing values in quantitative data analysing by Mixed model were imputed by statistical interpolation. In analysing bleeding, anal leakage and presence of prolapse in FAS population, missing data where either replaced using the LOCF method or imputed as positive (i.e., worst case). Results: 45 patients were enrolled. Data showed a significant reduction of discomfort in treated patients both during and after treatment (p<0.001 at all-time points evaluated), with a median VAS score decrease of 30 points after treatment when compared to baseline. The same significant reduction (p<0.001) was shown for all other symptoms either at the end of treatment or at earlier time points, both in PP and FAS populations. As for objective signs, a significant reduction was observed, at each time point compared to baseline, in the number of patients from the PP population positive for bleeding (p<0.001) and anal leakage (p<0.05). A similar evolution was shown in FAS population, where reduction was progressive over the 10-day treatment and statistically significant or almost significant irrespectively of imputation method used. In 6 out of 10 patients presenting prolapse at baseline, prolapse was no more evident after treatment. No treatment-related adverse events were registered. Conclusion: The class IIb medical device made of substances under study is a valid, highly tolerated and safe therapeutic option in medical management of grade I and II HD. Trial registration NCT03545724 2018.06.04.