E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
small bowel angiodysplasias |
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E.1.1.1 | Medical condition in easily understood language |
vascular malformations in the small bowel |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to determine if octreotide significantly decreases the iron infusion or blood transfusion requirement in patients who have refractory anemia due to recurrent gastrointestinal bleeding from small bowel angiodysplasias despite endoscopic intervention. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to investigate whether octreotide prevent the number of rebleeds and thereby increases the haemoglobin level. The third objective is to assess safety of octreotide in a dosage of 40 mg per 4 weeks. With the follow-up data epidemiologic knowledge will be provided. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with refractory anaemia due to gastrointestinal bleeding from small bowel angiodysplasias without any other possible source of bleeding, who are blood transfusion or iron infusion dependent despite endoscopic intervention and oral iron supplementation.
1. Diagnosis of angiodysplasia is made by upper, lower gastrointestinal endoscopy and video capsule or enteroscopy. Single or multiple 2–5 mm flat bright red spots with round uniform or slightly irregular margins, or lesions appearing as raised and reddened areas with a distinctly irregular margin, when larger than 5 mm are seen.
2. Transfusion dependent: at least 2 blood transfusions or iron infusions in the 6 months before inclusion, despite an attempt to supplement iron orally.
3. Failure of endoscopic therapy: at least one attempt with single balloon enteroscopy or dubbel balloon enteroscopy to coagulate the angiodysplasias with APC within the year of diagnosis of symptomatic AD.
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E.4 | Principal 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 blood transfusion dependency)
- patients with chronic renal failure who have a GFR < 30 ml/min
- 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
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E.5 End points |
E.5.1 | Primary end point(s) |
The percentual decrease in blood and iron requirements between the year prior to inclusion and the treatment period of one year. Percentual decrease =
(number of blood transfusions and iron infusions in the year prior to inclusion -
number of blood transfusions and iron infusions during the study period ) / number of blood and iron infusions in the year prior to inclusion.
The percentual decrease will be 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.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After finishing the last follow-up of the last patient (week 60). We will make a comparison between different time intervals in between this period. |
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E.5.2 | Secondary end point(s) |
- Percentage of hemoglobin increase from baseline until end of treatment for patients treated with octreotide compared to the control group
- The mean difference in hemoglobin level from baseline until end of treatment for patients treated with octreotide compared to the control group
- Number of patients requiring red blood cell transfusions from baseline until end of treatment for patients treated with octreotide compared to the control group
- Number of patients requiring other transfusions or medication to correct coagulation between baseline until end of treatment for patients treated with octreotide compared to the control group (see ‘standard of care’)
- The change in number and severity of bleeding episodes (see for definition section 4.3.2) between start and end of treatment for patients treated with octreotide compared to the control group
- The change in number of patients free of rebleeding between start and end of treatment for patients treated with octreotide compared to the control group
- Reduction in oral iron requirement between start and end of treatment for patients treated with octreotide compared to the control group (see for definition section 4.3.3 “standard of care”)
- The change in level of serum ferritin between baseline until end of treatment for patients treated with octreotide compared to the control group
- The number and type of adverse events (cardiac, pulmonary, neurological, other) between the control and treatment arm during the treatment period F(1)
- Difference in number of hospitalizations, ICU admissions and duration of hospitalization between the control and treatment arm during the treatment period F(1)
- The need for rescue therapy using argon plasma coagulation, coiling or surgery compared between the control and treatment arm during the treatment period F(1)
- Change in Quality of Life as measured by SF36 and PSQ-An questionnaire between baseline and end of treatment for patients treated with octreotide compared to the control group
- Mortality and cause of death compared between the control and treatment arm during the treatment period
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Saftey endpoints will be analysed after the inclusion of 15 patients or after 6 months after the start of the study. And after the end of the study. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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A interim-analysis will be performed on the primary endpoint after a half year. DSMB decides upon the continuation of the trial. The Peto approach is used for beneficial effect. For harm (higher incidence of AEs in the octreotide group) no stopping rule is chosen. In a meeting(s) of both the DSMB and steering committee any increase in AEs in the octreotide arm will be discussed to see whether a causative relation may be present and in light of the international literature. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |