The Efficacy of Aescin in Combination With Micronized Purified Flavonoid Fraction (MPFF) in the Control of Bleeding and Prevent Recurrence of Acute Internal Hemorrhoids, A Randomized Controlled Trial, A Pilot Study

Hemorrhoidal disease, characterized by symptomatic enlargement and distal displacement of anal cushions, has been a subject of recognition and management for centuries. The etymology of "hemorrhoid" is traced back to the Greek words haima (blood) and rhoos (flow). Prevalent in over 20% of the population across various life stages, this anorectal condition impacts both genders. The multifaceted development of the disease incorporates theories encompassing abnormal dilation of hemorrhoidal plexuses, distension of arteriovenous anastomoses, prolapse of anal pads, and a myriad of genetic, anatomical, dietary, and lifestyle factors. Manifestations range from venous distension to bleeding and thrombosis, with classification based on location (internal/external/combined) and degree of prolapse (grade 1-4).

Upon comprehensive history-taking and examinations, including digital rectal and proctoscope assessments, a definitive diagnosis is established, leading to the treatment phase. Although outpatient procedures demonstrate efficacy, patients may persist with pain and discomfort. Medical intervention assumes significance for stages 1 and 2, incorporating approaches such as rubber-band ligation, injection sclerotherapy, and dietary modifications. Micronized Purified Flavonoid Fraction (MPFF), integral to hemorrhoid treatment, has been scrutinized for its ability to mitigate pathogenic processes culminating in acute bleeding[8]. The stagnation of blood in vascular plexuses prompts an inflammatory response, activating white cells and increasing vessel wall permeability. MPFF's flavonoid compounds are posited to alleviate bleeding by augmenting venous tone, reducing stasis, inhibiting inflammatory mediators, and enhancing lymphatic drainage. Multiple trials substantiate MPFF's efficacy in ceasing bleeding, alleviating symptoms, and preventing hemorrhoid relapse. A recent randomized controlled trial shows that MPFF can cease bleeding hemorrhoids in 3 to 4 days.

Aescin, a saponin mixture found in Aesculus hippocastanum (horse chestnut). The primary active component, β-aescin, contributes to the plant's medicinal attributes. Experimental investigations in animal models underscore its anti-edematous, anti-inflammatory, and venotonic properties, attributed to molecular mechanisms facilitating ion entry into channels and elevating venous tension. In the past, we used aescin for hemorrhoid treatment benefit in reducing mass effect with control bleeding postoperative hemorrhoidectomy. Based on our previous project (SUR-2567-0150), the combination of aescin with MPFF has demonstrated significant efficacy in stopping bleeding and reducing the mass effect in Grade 1 and 2 hemorrhoids. We aim to study the long-term effects of this combination over 1, 3, and 6 months. This study seeks to provide valuable insights that could inform and refine therapeutic strategies for managing hemorrhoids, ultimately improving patient outcomes

Study Overview

• Status: Enrolling by invitation
• Conditions: Hemorrhoid
• Intervention / Treatment: Drug: MPFF; Drug: Aescin in Horse Chestnut

Detailed Description

Hemorrhoidal disease, characterized by symptomatic enlargement and distal displacement of anal cushions, has been a subject of recognition and management for centuries. The etymology of "hemorrhoid" is traced back to the Greek words haima (blood) and rhoos (flow). Prevalent in over 20% of the population across various life stages, this anorectal condition impacts both genders. The multifaceted development of the disease incorporates theories encompassing abnormal dilation of hemorrhoidal plexuses, distension of arteriovenous anastomoses, prolapse of anal pads, and a myriad of genetic, anatomical, dietary, and lifestyle factors. Manifestations range from venous distension to bleeding and thrombosis, with classification based on location (internal/external/combined) and degree of prolapse (grade 1-4).

Upon comprehensive history-taking and examinations, including digital rectal and proctoscope assessments, a definitive diagnosis is established, leading to the treatment phase. Although outpatient procedures demonstrate efficacy, patients may persist with pain and discomfort. Medical intervention assumes significance for stages 1 and 2, incorporating approaches such as rubber-band ligation, injection sclerotherapy, and dietary modifications. Micronized Purified Flavonoid Fraction (MPFF), integral to hemorrhoid treatment, has been scrutinized for its ability to mitigate pathogenic processes culminating in acute bleeding[8]. The stagnation of blood in vascular plexuses prompts an inflammatory response, activating white cells and increasing vessel wall permeability. MPFF's flavonoid compounds are posited to alleviate bleeding by augmenting venous tone, reducing stasis, inhibiting inflammatory mediators, and enhancing lymphatic drainage. Multiple trials substantiate MPFF's efficacy in ceasing bleeding, alleviating symptoms, and preventing hemorrhoid relapse. A recent randomized controlled trial shows that MPFF can cease bleeding hemorrhoids in 3 to 4 days.

Aescin, a saponin mixture found in Aesculus hippocastanum (horse chestnut). The primary active component, β-aescin, contributes to the plant's medicinal attributes. Experimental investigations in animal models underscore its anti-edematous, anti-inflammatory, and venotonic properties, attributed to molecular mechanisms facilitating ion entry into channels and elevating venous tension. In the past, we used aescin for hemorrhoid treatment benefit in reducing mass effect with control bleeding postoperative hemorrhoidectomy. Based on our previous project (SUR-2567-0150), the combination of aescin with MPFF has demonstrated significant efficacy in stopping bleeding and reducing the mass effect in Grade 1 and 2 hemorrhoids. We aim to study the long-term effects of this combination over 1, 3, and 6 months. This study seeks to provide valuable insights that could inform and refine therapeutic strategies for managing hemorrhoids, ultimately improving patient outcomes

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Thailand
  • Maung
    • Chiangmai, Maung, Thailand, 50200
      • Chiangmai University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Acute active bleeding hemorrhoid grade 1 and 2 with in 7 days
• Age over 20 years
• In patients aged over 50 years, it is imperative to confirm the absence of any alternative causes of bleeding through a colonoscopy
• Can follow up in 6 months

Exclusion Criteria:

• Bleeding disorder
• History of colorectal cancer, inflammatory bowel disease, portal hypertension, chronic kidney disease grade 3 or over
• Patient required other treatment such as hemorrhoidectomy or RBL
• Patient who received antiplatelet or anticoagulant
• Physical exam reveals anal fissure
• Pregnancy
• Any psychotic disorder
• Refuse to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: MPFF + Placebo; Patient will recived MPFF 3000 mg for 7 day then 1000 mg for 2 month + placebo	Drug: MPFF; MPFF 3000 mg 7 day then 1000 mg 2 months
Active Comparator: MPFF + Aescin; Patient will recived MPFF 3000 mg for 7 day then 1000 mg for 2 month + Aescin 60 mg for 2 month	Drug: MPFF; MPFF 3000 mg 7 day then 1000 mg 2 months; Drug: Aescin in Horse Chestnut; Patient will recived MPFF 3000 mg for 7 day then 1000 mg for 2 month + Aescin 60 mg for 2 month

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence of hemorrhoid	Present of bleeding or protuding mass in1 3 6 month	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stop bleeding in acute phase	Compare efficacy of bleeding cessation in 7 day	7 day

Collaborators and Investigators

• Sponsor: Chiang Mai University
• Investigators: Principal Investigator: WITCHA VIPUDHAMORN, MD, Division of Colorectal Surgery, Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: December 19, 2024
• First Submitted That Met QC Criteria: December 19, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: hemorrhoid; MPFF; Asecin
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Disease Attributes; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Rectal Diseases; Recurrence; Hemorrhoids
• Other Study ID Numbers: SUR-2567-0485

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all IPD that underlie results in a publication
• IPD Sharing Time Frame: 6 months
• IPD Sharing Access Criteria: contact via email
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No