Efficacy of Octreotide on Blood and Iron Requirements in Patients With Anemia Due to Angiodysplasias

Anemia Clinical Trial

— OCEAN  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02384122
• Other study ID #: NLOCEAN.50514.091.14
• Status: Completed
• Phase: Phase 3
• Start date: September 2015
• Est. completion date: May 2023

Study information

• Verified date: April 2023
• Source: Radboud University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: May 2023
• Est. primary completion date: July 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Anemia
• Angiodysplasia
• Gastrointestinal Hemorrhage
• Hemorrhage
• Vascular Malformations

Intervention

Drug:
• Octreotide
Two injections of 20 mg will be given monthly.

Locations

Country	Name	City	State
Netherlands	Jeroen Bosch Hospital	's-Hertogenbosch	Noord-Brabant
Netherlands	Gelre Hospital	Apeldoorn	Gelderland
Netherlands	Rijnstate Hospital	Arnhem
Netherlands	Reinier de Graaf Gasthuis	Delft	Zuid-Holland
Netherlands	Catharina Hospital	Eindhoven	Noord-Brabant
Netherlands	University Medical Center Groningen (UMCG)	Groningen
Netherlands	Tjongerschans Hospital	Heerenveen
Netherlands	St. Antonius Hospital	Nieuwegein	Utrecht
Netherlands	Radboud University Medical Center (Radboudumc)	Nijmegen	Gelderland
Netherlands	Maasstad Hospital	Rotterdam
Netherlands	Elisabeth-TweeSteden Hospital	Tilburg	Noord-Brabant
Netherlands	Bernhoven Hospital	Uden

Sponsors (12)

Lead Sponsor	Collaborator
Radboud University Medical Center	Bernhoven Hospital, Catharina Ziekenhuis Eindhoven, Elisabeth-TweeSteden Ziekenhuis, Gelre Hospitals, Jeroen Bosch Ziekenhuis, Maasstad Hospital, Reinier de Graaf Groep, Rijnstate Hospital, St. Antonius Hospital, Tjongerschans hospital, University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Subgroup analyses on blood transfusion dependency	Analyses include all patients that required at least one red blood cell transfusion (per 500 ml or packed cells) in the year before randomization (52 weeks).	Study year (52 weeks)
Other	Subgroup analyses on use of antithrombotics	Analyses include all patients that required at least one form of antithrombotics in the year before randomization (52 weeks).	Study year (52 weeks)
Primary	Difference in blood and parenteral iron requirements (transfusion units)	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 standard of care arm, corrected for baseline transfusion requirements and follow-up time.	Study year (52 weeks)
Secondary	Proportion with a good treatment response	The proportion of patients in both groups that experienced a =50% (defined as a good response) and 100% (defined as a full response) reduction in the number of transfusion units received during the study year compared to baseline	During the study year (52 weeks) compared to the year (52 weeks) before randomization
Secondary	Use of concomitant care	The proportion of patients in both groups that required concomitant care. Concomitant care consists of application of APC, discontinuation of antithrombotics, use of tranexamic acid, and starting octreotide in the control group.	Study year (52 weeks)
Secondary	Difference in endoscopic procedures	The mean difference in endoscopic procedures between both groups.	Study year (52 weeks)
Secondary	Difference in bleeding episodes	The mean difference in bleeding episodes between both groups. A bleeding episode is defined as each non-contiguous episode in which hospital care is sought for anemia.	Study year (52 weeks)
Secondary	Difference in healthcare utilization	The mean difference in healthcare utilization between both groups. Healthcare utilization consists of hospital admissions, ambulatory care, and emergency care.	Study year (52 weeks)
Secondary	Difference in hemoglobin levels	The mean difference in serum hemoglobin levels (mmol/L) between both groups.	Study year (52 weeks)
Secondary	Difference in ferritin levels	The mean difference in serum ferritin levels (ug/L) between both groups.	Study year (52 weeks)
Secondary	Difference in fatigue levels	The mean difference in fatigue levels between both groups. Fatigue is a patient-reported outcome measure (PROM), measured by the Multidimensional Fatigue Inventory (MFI-20), which covers five dimensions of fatigue affect and -tolerability. MFI-20 scores range from 20 (best) to 100 (worst).	Study year (52 weeks)
Secondary	Difference in quality of life	The mean difference in quality of life between both groups. Quality of life is a patient-reported outcome measure (PROM), measured by the Short Form Health Survey (SF-36), which uses eight subdomains to evaluate physical- and mental health. SF-36 scores range from 0 (worst) to 100 (best).	Study year (52 weeks)
Secondary	Difference in adverse events	The proportion of patients in both groups that experienced at least one adverse event (AE).	Study year (52 weeks)
Secondary	Difference in serious adverse events	The proportion of patients in both groups that experienced at least one serious adverse event (SAE).	Study year (52 weeks)
Secondary	Difference in mortality	The proportion of patients in both groups that died during the study.	Study year (52 weeks)

External Links

•   Announcement of research project in the "Nederlands Tijdschrift voor Geneeskunde"