Hereditary hemorrhagic telangiectasia (HHT), also known as Osler– Weber–Rendu disease (in specific patients with gastrointestinal bleedings)
Conditions
Interventions
Pharmaceutical Form: Solution for injection
CAS Number: 79517-01-4
Other descriptive name: OCTREOTIDE ACETATE
Sponsors
Radboudumc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria: • Patients older than 18 years with written informed consent. • Diagnosis of HHT: either confirmed by genetic testing or the Curaçao criteria (definite diagnosis) (7). • Presence of endoscopic proven GI AVM manifestations / telangiectasias confirmed within the last 12 months (upper and/or lower endoscopy and/or capsule endoscopy). • Endoscopic refractory: at least 1 endoscopic APC, laser, or other endoscopic treatment modality performed in the past 5 years. • Diagnosis of iron deficiency anemia (IDA). IDA is defined as: o At least one serum ferritin below =65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: • Liver cirrhosis Child-Pugh C, • Insulinoma, • Uncontrolled diabetes mellitus as defined by HbA1c >64 mmol/ml, despite adequate therapy, • Juvenile Polyposis Syndrome • Symptomatic cholecystolithiasis (possible side-effect octreotide) Chronic or acute pancreatitis • Bradycardia (heart rate below 50)* • Hypersensitivity to the active ingredient (octreotide) or to auxiliary materials of the study medication • Severe disease/comorbidities with a life expectancy < 1 year • Use of chemotherapy and / or ciclosporin • Pregnancy or nursing women or women who have a pregnancy wish during the study period. • Women of childbearing potential who do not have a confirmed menstrual period and a negative, highly sensitive urine or serum pregnancy test < 7 days before inclusion • Women of childbearing potential who do not use a highly effective contraceptive measure (according to section 4.1 of the Recommendations related to contraception and pregnancy testing in clinical trials of the Heads of Medicines Agencies (HMA)) or refuse to maintain this measure during the entire treatment-and relevant systemic exposure period.(25) • Women of childbearing potential who refuse to undergo additional pregnancy testing during the treatment period • Use of other anti-angiogenic drug treatment (thalidomide and/or bevacizumab • Use of hormonal (estrogen) therapy and/or antifibrinolytic therapy (tranexamic acid) to treat anemia due to telangiectasia with sufficient effect. However, when patients are red blood cell transfusion or iron infusion dependent despite these treatment options and are naïve to octreotide treatment, patients are still eligible for inclusion. *If a patient has a heart rate below 60 and uses cardiovascular medication that affect the heart rate (e.g. beta blockers and calcium channel blockers) the prescribing specialist (or another competent specialist) will be consulted about the possibility to adjust the dose of these medicines. Patients with a heartrate below 50 (despite dose adjustments) will be excluded from participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effectiveness of somatostatin analogues in decreasing the transfusion requirements in patients with HHT and GI bleeding who are refractory to endoscopic therapy.;Secondary Objective: Investigate the effectiveness of octreotide on: decreasing the endoscopic treatment frequency, increasing the quality of life, decreasing fatigue and epistaxis symptoms and costeffectiveness.;Primary end point(s): The difference in the number of patients in the treatment arm and the number of patients in the observational arm with a ‘successful response’. A successful response is defined as a decrease of =50% in the number of red blood cell transfusions and/or number of IV iron infusions (per 500mg) given between baseline period (26 weeks prior to study inclusion) and during the treatment study period (26 weeks). Patients who do not have a successful response (patients with a decrease of <50%) will be counted as treatment failures. NB Patients who exclusively or primarily used IV iron infusions at baseline and required (more) red blood cell transfusions during the treatment study period will be counted as treatment failures regardless of their percentual decrease in IV iron infusions. Patients who exclusively or primarily used red blood cell transfusions at baseline and required (more) iron infusions during the treatment study period will be counted as treatment failures if their total number of red blood cell transfusions and iron infusions during the treatment study period exceeds half of the total number of red blood cell transfusions (and iron infusions) during baseline. NB The exact preparation and dosage of IV iron infusions should be noted for each infusion. The preparation of IV iron should be kept consistent at baseline and during study period.;Timepoint(s) of evaluation of this end point: 26 weeks prior to study inclusion and during the treatment study period (26 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The absolute mean and median difference and the percentage mean and median difference between baseline (26 weeks prior to study inclusion) and the treatment study period (26 weeks) of patients in the treatment arm compared to patients in the observational arm in: - Number of red blood cell transfusions - Number of Intravenous iron infusions (per 500mg) - Number of endoscopic treatments The absolute mean and median difference and the percentage mean and median difference at baseline (< 7 days before inclusion) and after 4 weeks, 12 weeks, and 26 weeks of the study period between patients in the treatment arm and patients in the observational arm in the value of: - Hemoglobin and ferritin levels The absolute mean and median difference and the percentage mean and median difference between baseline (26 weeks prior to study inclusion) and the treatment study period (26 weeks) of patients in the treatment arm compared to patients in the observational arm in: - Patient reported outcome measures (PROMS): which include quality of life (measured by the SF-36), level of fatigue (measured by the multidimensional fatigue inventory (MFI)-20) and epistaxis severity (measured by the ESS tool). The absolute mean and median difference and the percentage mean and median difference in the number of (S)AE’s during the treatment study period (26 weeks) between patients in the treatment arm and patients in the observational arm. The absolute mean and median difference and the percentual mean and median difference between baseline (26 weeks prior to study inclusion) and the treatment study period (26 weeks) of patients in the treatment arm compared to patients in the observational arm in cost effectiveness. Cost effectiveness will be defined by measuring the healthcare costs. The following volumes of healthcare will be registering in Case Record Forms (CRF): (co) medication, visits and consultations to specialists or other health care professionals, lab and imagine | — |
Countries
France, Germany, Italy, Netherlands, United Kingdom
Contacts
Public ContactLia Goltstein
Radboudumc
Outcome results
None listed