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

• ClinicalTrials.gov Identifier: NCT02874326
• Recruitment Status: Unknown
• First Posted: August 22, 2016
• Last Update Posted: April 20, 2018
• Sponsor: Radboud University Medical Center
• Collaborator: St. Antonius Hospital
• Information provided by (Responsible Party): Radboud University Medical Center

Tracking Information

• First Submitted Date: August 17, 2016
• First Posted Date: August 22, 2016
• Last Update Posted Date: April 20, 2018
• Actual Study Start Date: October 2016
• Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 17, 2016)

The percentage of patients who are full responder, partial responder and non-responder at the end of the treatment period [ Time Frame: Comparing the 6 months before inclusion and the study period (26 weeks) ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 22, 2016)

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

Original Secondary Outcome Measures (submitted: August 17, 2016)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Octreotide in Patients With GI Bleeding Due to Rendu-Osler-Weber
• Official Title: 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

Brief Summary

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.

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
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Hereditary Hemorrhagic Telangiectasia
• Gastrointestinal Hemorrhage
• Anemia

Intervention

Drug: Octreotide LAR

Other Names:

• Sandostatin
• Dutch registration number (RVG) 18236
• Anatomical Therapeutic Chemical (ATC) H01CB02

Study Arms

Experimental: Active comparator: Octreotide LAR

Sandostatin LAR Sandostatin LAR 20 mg will be administered once every 4 weeks as a intramuscular injection

Intervention: Drug: Octreotide LAR

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 17, 2016): 15
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2018
• Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT02874326
• Other Study ID Numbers: NLROW.1012.15
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Radboud University Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Radboud University Medical Center
• Original Study Sponsor: Same as current
• Collaborators: St. Antonius Hospital

Investigators

• Principal Investigator: Joost Drenth, MD PhD; Radboud University Medical Center

• PRS Account: Radboud University Medical Center
• Verification Date: April 2018