Study of Placebo or Bosentan to Treat Patients With Single Ventricle Physiology.

Brief Title

Study of Placebo or Bosentan to Treat Patients With Single Ventricle Physiology.

Official Title

Treatment With Endothelin Antagonist to Tcpc Patients; a Multicenter, Randomized, Prospective Study Measuring Maximal O2 Uptake in Ergometer Bicycle Test

Brief 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.
    

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Change from baseline in VO2max at 14 weeks

Secondary Outcome

 Change from baseline in blood samples at 14 weeks

Condition

Hypoplastic Left Heart Syndrome

Intervention

Bosentan

Study Arms / Comparison Groups

 Bosentan
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

75

Start Date

February 2011

Completion Date

March 2013

Primary Completion Date

March 2013

Eligibility 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
      

Gender

All

Ages

15 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Lars Sondergaard, DMSc, , 

Location Countries

Denmark

Location Countries

Denmark

Administrative Informations


NCT ID

NCT01292551

Organization ID

TEMPO study

Secondary IDs

2010-022389-28

Responsible Party

Principal Investigator

Study Sponsor

Rigshospitalet, Denmark

Collaborators

 Aarhus University Hospital

Study Sponsor

Lars Sondergaard, DMSc, Study Director, Rigshospitalet, Denmark


Verification Date

April 2013