Octreotide in Patients With GI Bleeding Due to Rendu-Osler-Weber (ROW)

An Uncontrolled, Pilot-study Assessing the Efficacy of Octreotide Long-acting Release to Decrease Transfusion Requirements and Endoscopy Frequency in Patients With Rendu-Osler-Weber and Gastrointestinal Bleeding

The purpose of this study is to determine whether long-acting octreotide is safe and effective in the treatment of patients with Rendu-Osler-Weber (e.g. HHT).

The study hypothesis is that octreotide is safe and will reduce transfusion requirements and endoscopy frequency in ROW patients with refractory anaemia due to bleeding gastrointestinal telangiectasias.

Study Overview

• Status: Unknown
• Conditions: Anemia; Gastrointestinal Hemorrhage; Hereditary Hemorrhagic Telangiectasia
• Intervention / Treatment: Drug: Octreotide LAR

Detailed Description

Rationale: Rendu-Osler-Weber (ROW) is an autosomal dominant hereditary disease which affects 1 / 5-8000 individuals. It is characterized by arteriovenous malformations (AVMs) and telangiectasias in multiple organs, including the gastrointestinal tract. Patients can be transfusion dependent due to severe gastrointestinal bleeding from those telangiectasias. Endoscopy is not as effective due to the recurrent character of the telangiectasias. Based on literature in patients with non-ROW AVMs and telangiectasias, octreotide might be beneficial for these patients to decrease their transfusion needs.

Objective: To assess the efficacy of octreotide in decreasing the need for transfusions and endoscopic intervention in patients ROW with refractory anaemia due to gastrointestinal bleeding telangiectasias.

Study design: Multicenter, open-label uncontrolled pilot study.

Study population: Patients with ROW and symptomatic gastrointestinal bleeding telangiectasias, who are transfusion and/or endoscopy dependent:

1. Transfusion dependent: at least 2 blood and/or iron infusions in the 6 months before inclusion.
2. Endoscopy dependent: at least one endoscopic intervention with argon plasma coagulation (APC) after the initial/first endoscopic treatment after diagnosis in the half year before inclusion or unsuitable for endoscopy.

Intervention: The intervention is 20 mg Sandostatin long-acting release (LAR) once every four weeks for 26 weeks on top of standard of care.

Main study parameters/endpoints: Primary outcome is response to treatment defined as:

• complete: no endoscopic intervention or transfusion requirements
• partial: a reduction in endoscopic intervention or transfusion requirements
• non-response: an equal or increase in endoscopy frequency or transfusions Important secondary outcomes are the percent change in the number of rebleeds from baseline to endpoint and the number of epistaxis episodes.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Radboudumc
  • Utrecht
    • Nieuwegein, Utrecht, Netherlands, 3430 EM
      • St Antonius hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with Rendu-Osler-Weber
• Symptomatic gastrointestinal bleeds out of telangiectasias
• Transfusion and / or endoscopy dependent:

Transfusion: at least 2 blood and/or iron infusions in the 6 months before inclusion.

Endoscopy: at least one endoscopy with APC after the initial endoscopic treatment after diagnosis in the half year before inclusion or unsuitable for endoscopic therapy.

Exclusion Criteria:

• liver cirrhosis Child-Pugh C or acute liver failure
• previous unsuccessful treatment with somatostatin analogues (SST) for the same indication (refractory anaemia due to telangiectasias) or current effective treatment with a somatostatin analogue
• severe diseases with life expectancy < 1 year
• patients with left ventricular assist devices (LVAD's)
• Symptomatic cholecystolithiasis (without cholecystectomy)
• pregnancy or nursing women or women who have a pregnancy wish in the study period or who use anticonception inadequate
• current chemotherapy
• patients with a known hypersensitivity to SST analogues or any component of the octreotide LAR formulations
• no understanding of Dutch or English

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active comparator: Octreotide LAR; Sandostatin LAR Sandostatin LAR 20 mg will be administered once every 4 weeks as a intramuscular injection	Drug: Octreotide LAR; Other Names: Sandostatin; Dutch registration number (RVG) 18236; Anatomical Therapeutic Chemical (ATC) H01CB02

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percentage of patients who are full responder, partial responder and non-responder at the end of the treatment period	Full responder: no endoscopy and no blood/iron transfusions during treatment period.; Partial responder: a decrease in number of blood/iron transfusions and/or endoscopy during the treatment period compared with the 6 months prior to inclusion.; Non-responder: no decrease in number of blood/iron transfusions and endoscopy during the treatment period compared with the 6 months prior to inclusion.	Comparing the 6 months before inclusion and the study period (26 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percentual decrease in blood and iron requirements		Comparing the 6 months prior to inclusion and the treatment period of 6 months.
The percentual decrease in the number of endoscopic interventions		Comparing the 6 months prior to inclusion and the treatment period of 6 months.
The mean/median decrease on the epistaxis severity score (ESS)	Comparing baseline and the end of treatment visit (week 26)	Comparing the 6 months prior to inclusion and the treatment period of 6 months.
Change in quality of life using the Short Form (SF)-36 questionnaire		Comparing baseline and end of treatment visit
The number, type and severity of adverse events		Study period

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: St. Antonius Hospital
• Investigators: Principal Investigator: Joost Drenth, MD PhD, Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Anticipated): July 1, 2018
• Study Completion (Anticipated): October 1, 2018

Study Registration Dates

• First Submitted: August 17, 2016
• First Submitted That Met QC Criteria: August 17, 2016
• First Posted (Estimate): August 22, 2016

Study Record Updates

• Last Update Posted (Actual): April 20, 2018
• Last Update Submitted That Met QC Criteria: April 18, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Octreotide; Somatostatin; Sandostatin LAR
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Congenital Abnormalities; Hematologic Diseases; Gastrointestinal Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Cardiovascular Abnormalities; Vascular Malformations; Hemorrhage; Telangiectasis; Gastrointestinal Hemorrhage; Telangiectasia, Hereditary Hemorrhagic; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Octreotide
• Other Study ID Numbers: NLROW.1012.15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No