Clinical trial NCT02874326: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hereditary Hemorrhagic Telangiectasia
Gastrointestinal Hemorrhage
Anemia
Keywords: Sandostatin LAR
Somatostatin
Octreotide
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: St. Antonius Hospital
First posted: 2016-08-22
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The percentage of patients who are full responder, partial responder and non-responder at the end of the treatment period
timeFrame: Comparing the 6 months before inclusion and the study period (26 weeks)
Secondary outcomes:
measure: The percentual decrease in blood and iron requirements
timeFrame: Comparing the 6 months prior to inclusion and the treatment period of 6 months.
measure: The percentual decrease in the number of endoscopic interventions
timeFrame: Comparing the 6 months prior to inclusion and the treatment period of 6 months.
measure: The mean/median decrease on the epistaxis severity score (ESS)
timeFrame: Comparing the 6 months prior to inclusion and the treatment period of 6 months.
measure: Change in quality of life using the Short Form (SF)-36 questionnaire
timeFrame: Comparing baseline and end of treatment visit
measure: The number, type and severity of adverse events
timeFrame: Study period
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: Gelderland
city: Nieuwegein
country: Netherlands
facility: St Antonius Hospital
state: Utrecht
Study officials:
affiliation: Radboud University Medical Center
name: Joost Drenth, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: