The CHORMES (Use of mesoglycan in the acute phase of hemorrhoidal disease) trial is underway to evaluate the efficacy and safety of mesoglycan in patients with acute hemorrhoidal disease (HD). This randomized, double-blind, placebo-controlled study aims to determine if mesoglycan can effectively reduce symptoms and improve the quality of life for individuals suffering from Grade I–III HD or external thrombosed hemorrhoids.
The rationale behind using mesoglycan stems from its anti-edematous, antithrombotic, and profibrinolytic properties. Previous studies have suggested its potential clinical activity in patients with acute HD. The CHORMES trial seeks to provide a clearer assessment of mesoglycan's benefits compared to placebo, while allowing concomitant use of analgesics and stool softeners to reflect real-world clinical practice.
Trial Design and Intervention
The trial will enroll a total of 50 patients, with 25 patients in each treatment group. Participants will receive either mesoglycan or a placebo. Mesoglycan capsules contain 50 mg of mesoglycan sodium salt, comprising heparin sulfate (47.5%), dermatan sulfate (35.5%), chondroitin sulfate (8.5%), and heparin slow (8.5%), along with excipients. The placebo capsules contain only excipients.
The dosing regimen involves two capsules twice daily (200 mg total daily dose of mesoglycan) for the first 5 days, followed by one capsule twice daily (100 mg total daily dose of mesoglycan) for the subsequent 35 days. Patients may discontinue treatment at any time, either spontaneously or per the investigator's decision, based on their clinical condition. Early termination may also occur due to withdrawal of informed consent, protocol violations, or serious adverse events (AEs).
To ensure adherence, patients will return empty blister packs and unused medication at each assessment visit. Investigators will maintain accountability for all drugs dispensed and returned using a drug accountability form.
Permitted and Prohibited Concomitant Medications
Permitted concomitant medications include analgesics, stool softeners, fecal emollients, and treatments for unrelated conditions that do not interfere with the study drug. However, drugs that may interfere with the evaluation of the study drug or alter the evaluation of efficacy parameters are prohibited. These include oral anticoagulation therapy (e.g., warfarin, acenocoumarol), novel oral anticoagulants (e.g., rivaroxaban, apixaban, and dabigatran), and anti-platelet agents (e.g., double-anti-aggregation or acetylsalicylic acid > 160 mg/day and ticlopidine).
Primary and Secondary Outcomes
The primary objective of the trial is to demonstrate the superiority of mesoglycan versus placebo in reducing symptoms of HD, measured by the change in Hemorrhoidal Disease Symptom Score (HDSS) from baseline to day 40. The HDSS is a 5-item questionnaire assessing the frequency and severity of HD symptoms, with total scores ranging from 0 to 20 (higher scores indicate more severe symptoms).
Secondary objectives include assessing:
- Changes in Health-Related Quality of Life (HRQoL) from baseline to day 40 using the Short Health Scale for Hemorrhoidal Disease (Short Health ScaleHD).
- Safety (AEs, physical assessments, vital signs, and laboratory parameters).
- Fecal continence (using the Vaizey score).
- Bleeding (assessed via a study-defined bleeding score).
- The amount and type of analgesics taken (using frequency tables).
- Pain (measured using a visual analog scale [VAS]).
Assessments for secondary outcomes will occur at baseline, day 10, day 20, and day 40, except for fecal incontinence, which will be assessed only at baseline and day 40. Patients will also be questioned on day 70 (via telephone) regarding AEs. AEs occurring from signing the informed consent form until 30 days after the last administration of study drug or placebo will be recorded and classified according to the Medical Dictionary for Regulatory Activities.
Sample Size and Recruitment
The trial aims to enroll 50 patients (25 per treatment group). This sample size is based on an assumed between-group difference in HDSS score of 1.8 points with a standard deviation (SD) of 1.7, an alpha of 0.05, and a two-tailed t-test with 90% power. Recruitment will continue until the target sample size is reached or until October 10, 2024, whichever comes first.
