OCEAN: Efficacy of Octreotide on Blood and Iron Requirements in Patients With Anaemia Due to Angiodysplasias

Sponsor

Radboud University Medical Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT02384122

Collaborator

St. Antonius Hospital (Other), Jeroen Bosch Ziekenhuis (Other), Amsterdam UMC, location VUmc (Other), Catharina Ziekenhuis Eindhoven (Other), Elisabeth-TweeSteden Ziekenhuis (Other), Gelre Hospitals (Other), Reinier de Graaf Groep (Other), Bernhoven Hospital (Other)

Enrollment

Locations

Arms

Duration (Months)

6.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether long-acting octreotide is effective in the treatment of patients with refractory anaemia due to angiodysplasias.

The hypothesis is that long-acting octreotide is effective in decreasing the blood and iron infusion requirements in those patients.

Condition or Disease	Intervention/Treatment	Phase
Angiodysplasia Vascular Malformations Gastrointestinal Hemorrhage Anemia	Drug: Octreotide	Phase 2/Phase 3

Detailed Description

Rationale:

Gastrointestinal angiodysplasias are an important cause of difficult to manage bleeding, especially in older patients. Angiodysplasias are technical challenging to manage endoscopic. Some patients are blood transfusion or iron infusion dependent due to rebleedings despite endoscopic intervention. In clinical practice we face difficulties in these patients as there is no known effective alternative treatment. In small cohort studies octreotide appears to decrease the bleeding episodes in those patients, but the evidence is still to weak to integrate this treatment modality in daily practice.

Objective:

To assess the efficacy of octreotide in decreasing the need for blood transfusions or iron infusion in patients with refractory anaemia due to gastrointestinal bleedings of angiodysplasias despite endoscopic intervention.

Study design:

Multicenter, randomized, open-label intervention study.

Study population:

62 patients, older than 45 years, with refractory anaemia due to bleeding of angiodysplasias without any other possible source of bleeding, who are blood transfusion or iron infusion dependent despite endoscopic intervention and oral iron supplementation.

Intervention:

Patients will be randomized (1:1) into two groups. The intervention group receives Octreotide 40 mg (Sandostatin LAR) once every four weeks for 48 weeks. The control group receives standard of care. The last follow-up visit is in week 60.

Main study parameters/endpoints:

The primary outcome is the percentual decrease in blood and iron requirements between the year prior to inclusion and the treatment period of one year. The percentual decrease will be compared between the intervention and control arm.

Important secondary outcomes are the percent change in the number of rebleeds from baseline to endpoint and the percentage of adverse events. An intention-to-treat analysis will be performed of the outcomes.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

62 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multicenter, Randomized, Open-label Clinical Trial Assessing the Efficacy of Octreotide in Decreasing Blood and Iron Requirements in Patients With Refractory Anaemia Due to Angiodysplasias

Study Start Date :

Sep 1, 2015

Anticipated Primary Completion Date :

Nov 1, 2019

Anticipated Study Completion Date :

Dec 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Octreotide Drug: Sandostatin LAR Sandostatin LAR 40 mg will be administered once every 4 weeks as a intramuscular injection	Drug: Octreotide Two injections of 20 mg will be given monthly. Other Names: Sandostatin LAR RVG 18236 ATC H01CB02
No Intervention: Standard of care Patients receive standard of care without a placebo.

Arm

Intervention/Treatment

Active Comparator: Octreotide

Drug: Sandostatin LAR Sandostatin LAR 40 mg will be administered once every 4 weeks as a intramuscular injection

Drug: Octreotide

Two injections of 20 mg will be given monthly.

Other Names:

Sandostatin LAR

RVG 18236

ATC H01CB02

No Intervention: Standard of care

Patients receive standard of care without a placebo.

Outcome Measures

Primary Outcome Measures

The mean difference in blood and iron requirements. [Comparing the one year before inclusion and the study period (until week 52)]
The mean/median difference in blood and iron requirements between the one year prior to inclusion and the treatment period of one year compared between the intervention and control arm. All blood transfusions that are given with another indication than gastrointestinal blood loss are registered, but excluded for analysis for the primary outcome.

Secondary Outcome Measures

Percentage of hemoglobin increase from baseline until end of treatment visit. [From inclusion in the study until end of treatment visit (week 48).]
Change in haemoglobin level comparing the octreotide the control arm, as assessed as slope through all haemoglobin measurements taken at study visits during the treatment phase.
Number of patients requiring red blood cell transfusions [From inclusion in the study until end of treatment (week 52).]
Comparing the octreotide with the control arm.
The mean difference in hemoglobin level [From inclusion in the study until end of treatment visit (week 48).]
Comparing the octreotide with the control arm.
Change in number and severity of bleeding episodes [From inclusion in the study until end of treatment visit (week 52).]
Comparing the octreotide with the control arm.
Number of patients free of rebleeding [The year prior to inclusion compared to the treatment period of one year (week 52).]
Comparing the octreotide with the control arm.
The number and type of adverse events [From inclusion in the study until last follow-up visit (week 60).]
Comparing the octreotide with the control arm.
Difference in number of hospitalizations, ICU admissions and duration of hospitalization [The year prior to inclusion compared to the treatment period of one year (week 52).]
Comparing the octreotide with the control arm.
Difference in need for rescue therapy [The year prior to inclusion compared to the treatment period of one year (week 52).]
Comparing the octreotide with the control arm for use of argon plasma coagulation, coiling or surgery.
Mortality and cause of death [From inclusion in the study until last follow-up visit (week 60).]
Comparing the octreotide with the control arm.
Difference in quality of life [From inclusion in the study until last follow-up visit (week 60).]
Quality of Life as measured by SF36 and PSQ-An questionnaire. Comparing the octreotide with the control arm.
Number of patients requiring other transfusions or medication to correct coagulation [From baseline until end of treatment (week 52).]
Comparing the octreotide with the control arm.
Percentual reduction in oral iron requirement [From baseline until end of treatment (week 52).]
Comparing the octreotide with the control arm.
The change in level of serum ferritin [From baseline until end of treatment visit (week 48).]
Comparing the octreotide with the control arm.
The percentual decrease in blood and iron infusions. [The year prior to inclusion compared to the treatment period of one year (week 52).]
The percentual decrease in blood and iron infusions between the intervention arm compared to the control group.

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

proven angiodysplasias, without any other possible source of gastrointestinal bleeding.
transfusion dependency: at least 4 blood transfusions or iron infusions in the year before inclusion, despite an attempt to supplement iron orally
failure of endoscopic therapy: at least one endoscopic attempt to coagulate the angiodysplasias or unsuitable for endoscopic procedures
providing informed consent
older than 45 years

Exclusion Criteria:

age < 45 years
liver cirrhosis Child-Pugh C, liver failure or diagnosed portal hypertension
previous unsuccessful treatment with octreotide for the same indication (refractory anaemia due to angiodysplasias)
current thalidomide treatment which is effective (no transfusion dependency)
severe diseases with life expectancy < 1 year
patients with left ventricular assist devices (LVAD's)
Rendu-Osler-Weber
pregnancy or nursing women
uncontrolled diabetes as defined by HbA1C >64 mmol/ml, despite adequate therapy
hereditary hemorrhagic diseases or haematological disorders with active treatment
patients with a known hypersensitivity to SST analogues or any component of the sandostatin LAR formulations
symptomatic cholecystolithiasis
non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with this study treatment
systemic cancer currently undergoing chemotherapy or radiation therapy
refusal to enter the study
no understanding of Dutch or English

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gelre Hospitals	Apeldoorn	Gelderland	Netherlands	7334 DZ
2	Radboudumc	Nijmegen	Gelderland	Netherlands	6525 GA
3	Jeroen Bosch Hospital	's-Hertogenbosch	Noord-Brabant	Netherlands	5200 ME
4	Catharina hospital	Eindhoven	Noord-Brabant	Netherlands	5623 EJ
5	St. Elisabeth Hospital	Tilburg	Noord-Brabant	Netherlands	5022 GC
6	VU Medical Center	Amsterdam	Noord-Holland	Netherlands	1007 MB
7	St Antonius Hospital	Nieuwegein	Utrecht	Netherlands	3430 EM
8	Reinier de Graaf Groep	Delft	Zuid-Holland	Netherlands
9	Bernhoven	Uden		Netherlands