Micronized Purified Flavonoid- Fraction (MPFF) in the Management of Radiation Proctitis

Study Overview
=================
Brief Summary
-----------------
national and multi-center trial for medical therapy of chronic radiation proctitis inducing anorectal bleedings

Detailed Description
-----------------
Radiation proctitis is an inflammation of rectal mucosa, a complication following radiation therapy for cancers of the prostate, cervix, uterus, bladder and other malignancies in the pelvic area. Around 20 % of radiation patients develop radiation proctitis. There is a significant lack of trial treatments for radiation proctitis, even more, the studies often are small and single center designed or case series. In 2 recent reviews pointing out the management of radiation proctitis (2018 and 2016) a summary of current options in therapy according to current scientific knowledge is given. Unfortunately, these studies are about interventional options with the serious risk of complication. Only little data and lack of significance in smaller series on conservative strategies are given. The goal of the trial is to implement a specific medication in the management and every grade of radiation proctitis - concomitant to eventual need of MMPF is described with potent anti-inflammatory mucosal capacity reducing bleeding, pain and urgency symptoms in patients with hemorrhoidal and/or postoperative symptoms. By using a placebo instead of comparative oral medications (with low evidence) this study might illustrate clinical significance of expected results as well as information on the natural history of radiation proctitis. The goal of the study is to compare the number of necessary interventions required to stop bleeding in chronic radiation proctitis in patients receiving MMPF in comparison to patients in the control group receiving Placebo within 12 months of medical treatment.

Official Title
-----------------
A Multicenter, Randomized, Double Blind Placebo Controlled Trial of Micronized Purified Flavonoid- Fraction (MPFF) in the Management of Radiation Proctitis

Conditions
-----------------
Proctitis Radiation

Intervention / Treatment
-----------------
* Drug: MMPF (Micronized purified Flavonoid-Fraction)
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: signed informed consent form male and female patients age ≥ 18 years patients with diagnosis of radiation proctitis with macroscopic bleeding end of radiotherapy ≥ 3 month = 90 days ago Exclusion Criteria: infectious proctitis ulcerative proctitis (inflammatory bowel disease) persons unable to understand the informed consent persons, who are in dependent relationship with the study investigators or Sponsor pregnant or lactating women participation in an interventional study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a multicenter, randomized, double-blind, placebo-controlled Phase III study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational<br>Patients receive MMPF 500mg for one year | Drug: MMPF (Micronized purified Flavonoid-Fraction)<br>* 500mg film-coated tablet, oral route, tablets should be taken at meal times. 4-day course of 6 tablets daily, followed by 4 tablets over the next 3 days followed by 2 tablets daily, one at midday and one in the evening<br>|
| Placebo Comparator: Placebo<br>Patients receive Placebo for one year | Other: Placebo<br>* 4-day course of 6 tablets daily, followed by 4 tablets over the next 3 days followed by 2 tablets daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of necessary intervention | Interventions to stop acute bleeding by chronic radiation proctitis: surgical, endoscopic or proctoscopic interventions | Day 1- Day 360 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life of patients | Differences in quality of life of patients will be measured with evaluation of two questionnaires (EORTC QLQ C30 & PRT20). Higher scores mean a better quality of life. | Day 0 Day 180 Day 360 | 
| Blood samples | Differences in serum hemoglobin, thrombocytes, coagulation parameters (quick/pt=prothrombin time) | Day 0-Day 360 | 
| Stool | Differences in calprotectin stool level | Day 0-Day 360 | 
| Presence of histological alterations | Differences in histological alterations (distortion of crypts, Inflammation of crypts, fibrosis and ectasia of vessels, cytokines) | Day 0-Day 360 |