Study of Placebo or Bosentan to Treat Patients With Single Ventricle Physiology.
Information source: Rigshospitalet, Denmark
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hypoplastic Left Heart Syndrome; Tricuspid Atresia; Other Specified Congenital Anomalies of Heart
Intervention: Bosentan (Drug); Placebo (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Rigshospitalet, Denmark Official(s) and/or principal investigator(s): Lars Sondergaard, DMSc, Study Director, Affiliation: Rigshospitalet, Denmark Anders H Hebert, MD, Principal Investigator, Affiliation: Rigshospitalet, Denmark
Summary
The purpose of this study is to determine whether Bosentan is an effective and safe
treatment to adolescent and adult (15 years and older) patients, born with one ventricle of
the heart instead of two (single ventricle physiology) and who have undergone TCPC as a
palliative surgical treatment. The aim of the TCPC operation is to use the one functioning
ventricle to pump the blood flow to the body, while the blood to the lungs is received
directly from the caval veins, and is thus a passive flow, without the aid of a ventricle to
actively pump the blood through the pulmonary circulation. The resistance in the pulmonary
circulation is therefore critical to these patients. These patients have markedly lower work
capacity in bicycle test than the general public. Furthermore they have a high risk of
developing complications e. g. loss of protein from the intestines.
Bosentan is a medication that lowers the resistance in the pulmonary circulation. It is
routinely used for patients with pulmonary hypertension. Some studies have shown that drugs
that lower the pulmonary resistance can increase exercise capacity significantly in patients
with single ventricle physiology.
In this study 80 patients will receive either placebo or Bosentan for 14 weeks. Before and
after the treatment, bicycle test along with blood samples, stool samples and quality of
life interviews will be performed. Every four weeks during the study blood samples, physical
exam and interviews will be performed to ensure the safety of the treatment.
The investigators expect to find a significant increase in work capacity after 14 weeks in
the treatment group compared with the placebo group.
Moreover the investigators hope to find a decrease in intestinal protein loss and an
improved quality of life.
Clinical Details
Official title: Treatment With Endothelin Antagonist to Tcpc Patients; a Multicenter, Randomized, Prospective Study Measuring Maximal O2 Uptake in Ergometer Bicycle Test
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: Change from baseline in VO2max at 14 weeks
Secondary outcome: Change from baseline in blood samples at 14 weeksChange from baseline in SF36 questionnaire score at 14 weeks Change from baseline in feces alfa 1 antitrypsin at 14 weeks Number of participants with adverse events Change from baseline in vital signs Change from baseline in control blood samples Change from baseline in cardiac output/pulmonary blood flow
Detailed description:
In the statistical analysis the investigators wish to analyse interactions between the
primary endpoint and predefined subgroups in order to distinguish responders from
non-responders to the treatment. The predefined subgroups are:
NT-proBNP > 100 (yes/no) Ventricular anatomy (RV/LV) CT-proEndothelin-1. In the latter, the
investigators do not wish to predefine a specific value, due to limited experience with this
analysis. We wish to use the data from the study to find a cut-off value, that is able to
predict positive response to treatment.
Eligibility
Minimum age: 15 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- TCPC operated
- Age > 15 years old
- Clinical stability > 3 months, evaluated by investigator from clinical record
- For women: Negative s-hCG and use of contraception
Exclusion Criteria:
- Severe heart failure (NYHA-class IV)
- Oxygen saturation < 85 % at rest
- Pre-existing liver condition (transaminases 2x > reference)
- Renal failure (creatinin > 150 mmol/l)
- Obstruction of TCPC circulation
- History of work induced severe arrhythmia
- Systolic blood pressure below 80% of reference (BT < 88 mmHg)
- Use of any of following drugs: Fluconazol, Ketoconazole, CiclosporinA, Lopinavir,
Ritonavir, Rifampicin, Carbamazepin and Phenytoin
- Significant extra-cardiac condition e. g. neurological impairment
Locations and Contacts
Aarhus University Hospital, Aarhus 8200, Denmark
Rigshospitalet, Copenhagen 2100, Denmark
Lund University Hospital, Lund, Sweden
Karolinska Institutet, Stockholm, Sweden
Additional Information
Starting date: February 2011
Last updated: April 18, 2013
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