Clinical trial NCT02384122: Efficacy of Octreotide on Blood and Iron Requirements in Patients With Anemia Due to Angiodysplasias
Official title: A Multicenter, Randomized, Open-label Clinical Trial Assessing the Efficacy of Octreotide in Decreasing Blood and Iron Requirements in Patients With Refractory Anemia Due to Angiodysplasias
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Angiodysplasia
Vascular Malformations
Gastrointestinal Hemorrhage
Anemia
Keywords: Angiodysplasias
Sandostatin LAR
Gastrointestinal bleeding
Somatostatin analogs
Octreotide
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Jeroen Bosch Ziekenhuis
name: Elisabeth-TweeSteden Ziekenhuis
name: Catharina Ziekenhuis Eindhoven
name: Bernhoven Hospital
name: Tjongerschans hospital
name: Gelre Hospitals
name: Maasstad Hospital
name: Reinier de Graaf Groep
name: University Medical Center Groningen
name: Rijnstate Hospital
name: St. Antonius Hospital
First posted: 2015-03-10
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, open-label, randomized, parallel-group, superiority study to compare the efficacy of 40 mg octreotide long-acting release intramuscular every 28 days in addition to standard of care versus standard of care alone in patients with refractory anemia due to gastrointestinal bleeding from angiodysplasias.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether 40 mg octreotide long-acting release intramuscular every 28 days is effective in the treatment of patients with refractory anemia due to gastrointestinal angiodysplasias. We hypothesize that octreotide is effective in reducing the transfusion requirements (consisting of red blood cell transfusions and intravenous iron infusions) of patients with angiodysplasia-related anemia.

Detailed description: Rationale: Gastrointestinal angiodysplasias are a common source of intractable small bowel bleeding, especially in older patients. Endoscopic ablation of angiodysplasias has limited efficacy and rebleeding rates are substantial. Recurrent bleeding results in refractory anemia which is managed with blood transfusions and/or iron infusions. Transfusion dependency reduces quality of life and is associated with substantial cardiovascular morbidity and mortality. Small cohort studies suggest a beneficial effect of octreotide in bleeding angiodysplasias, but evidence from rigorous, well-controlled studies are lacking.

Objective: To assess the efficacy of octreotide in reducing the transfusion requirements (consisting of blood transfusions and iron infusions) of patients with refractory anemia due to gastrointestinal angiodysplasias despite endoscopic intervention.

Study design: Multicenter, randomized, open-label intervention study.

Study population: Patients aged 18 years or older with transfusion-dependent anemia due to endoscopically confirmed angiodysplasias. Transfusion units consist of iron infusions (of 500 milligrams \[mg\]) and red blood cell (RBC) transfusions. At least one endoscopic attempt to treat the angiodysplasias needs to be recorded unless contra-indications are present. Patients with liver cirrhosis Child-Pugh C or liver failure, uncontrolled diabetes mellitus (defined by a glycated hemoglobin \>64 mmol/mL), symptomatic cholecystolithiasis, and pregnant or nursing women, are regarded as ineligible because of the pharmacological profile of octreotide. Patients with hereditary hemorrhagic diseases or hematological disorders on active treatment, other alternative causes of gastrointestinal bleeding, presence of left ventricular assist devices, as well as patients with cancer under active treatment, and those with a life expectancy \<1 year are excluded from enrolment

Intervention: Patients will be randomized (1:1) into two groups. The intervention group receives 40 mg octreotide long-acting release (Sandostatin LAR) every 28 days for a total period of 52 weeks as an adjunct to standard of care. The control group receives standard of care along. The last follow-up visit is in week 60.

Main study parameters/endpoints: The primary endpoint is defined as the mean difference in blood (RBC transfusions per 500 ml or packed cells) and parenteral iron (IV iron infusions per 500 mg) requirements between the intervention and control group, corrected for baseline transfusion requirements and follow-up time.

Eligibility criteria: Inclusion criteria:

* Endoscopically diagnosed angiodysplasias
* Transfusion dependency: at least 4 red blood cell transfusions (per 500 ml or packed cells) and/or parental iron infusions (per 500 mg) in the year before inclusion
* Failure of endoscopic therapy: at least one endoscopic attempt to coagulate the angiodysplasias or unsuitable for endoscopic procedures
* Providing informed consent
* Older than 18 years

Exclusion Criteria:

* Liver cirrhosis Child-Pugh C, liver failure or diagnosed portal hypertension
* Previous treatment with octreotide for the same indication (refractory anemia due to angiodysplasias)
* Current thalidomide treatment which is effective (no transfusion dependency)
* Life expectancy \< 1 year
* Left ventricular assist devices (LVAD's)
* Hereditary hemorrhagic diseases or hematological disorders with active treatment
* Pregnancy or nursing women
* Uncontrolled diabetes as defined by HbA1C \>64 mmol/ml, despite adequate therapy
* Known hypersensitivity to somatostatin analogs
* Symptomatic cholecystolithiasis
* Systemic cancer under active treatment (chemotherapy or radiation therapy)

Primary outcomes:
measure: Difference in blood and parenteral iron requirements (transfusion units)
timeFrame: Study year (52 weeks)
Secondary outcomes:
measure: Proportion with a good treatment response
timeFrame: During the study year (52 weeks) compared to the year (52 weeks) before randomization
measure: Use of concomitant care
timeFrame: Study year (52 weeks)
measure: Difference in endoscopic procedures
timeFrame: Study year (52 weeks)
measure: Difference in bleeding episodes
timeFrame: Study year (52 weeks)
measure: Difference in healthcare utilization
timeFrame: Study year (52 weeks)
measure: Difference in hemoglobin levels
timeFrame: Study year (52 weeks)
measure: Difference in ferritin levels
timeFrame: Study year (52 weeks)
measure: Difference in fatigue levels
timeFrame: Study year (52 weeks)
measure: Difference in quality of life
timeFrame: Study year (52 weeks)
measure: Difference in adverse events
timeFrame: Study year (52 weeks)
measure: Difference in serious adverse events
timeFrame: Study year (52 weeks)
measure: Difference in mortality
timeFrame: Study year (52 weeks)
Other outcomes:
measure: Subgroup analyses on blood transfusion dependency
timeFrame: Study year (52 weeks)
measure: Subgroup analyses on use of antithrombotics
timeFrame: Study year (52 weeks)
Locations:
city: Apeldoorn
country: Netherlands
facility: Gelre Hospital
state: Gelderland
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center (Radboudumc)
state: Gelderland
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Hospital
state: Noord-Brabant
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
state: Noord-Brabant
city: Tilburg
country: Netherlands
facility: Elisabeth-TweeSteden Hospital
state: Noord-Brabant
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
state: Utrecht
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
state: Zuid-Holland
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital
city: Groningen
country: Netherlands
facility: University Medical Center Groningen (UMCG)
city: Heerenveen
country: Netherlands
facility: Tjongerschans Hospital
city: Rotterdam
country: Netherlands
facility: Maasstad Hospital
city: Uden
country: Netherlands
facility: Bernhoven Hospital
Study officials:
affiliation: Radboud University Medical Center
name: Joost Drenth, MD. PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Grooteman KV, van Geenen EJ, Drenth JP. Multicentre, open-label, randomised, parallel-group, superiority study to compare the efficacy of octreotide therapy 40 mg monthly versus standard of care in patients with refractory anaemia due to gastrointestinal bleeding from small bowel angiodysplasias: a protocol of the OCEAN trial. BMJ Open. 2016 Sep 12;6(9):e011442. doi: 10.1136/bmjopen-2016-011442.