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

April 18, 2013 updated by: Anders Hebert, Rigshospitalet, Denmark

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

75

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aarhus, Denmark, 8200
        • Aarhus University Hospital
      • Copenhagen, Denmark, 2100
        • Rigshospitalet
  • Sweden
      • Lund, Sweden
        • Lund University Hospital
      • Stockholm, Sweden
        • Karolinska Institutet

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Placebo tablets 2 x daily for 2 weeks, then change to different placebo tablets to match Bosentan group, 2 x daily for 12 weeks
Active Comparator: Bosentan
Drug: Bosentan
tablets Bosentan 62,5 mg x 2 daily for two weeks, then 125 mg x 2 daily for 12 weeks
Other Names:
  • Bosentan: Tracleer

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in VO2max at 14 weeks
Time Frame: Baseline and 14 weeks
Maximal O2 uptake in ml/min/kg in ergometer bicycle test
Baseline and 14 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in blood samples at 14 weeks
Time Frame: Baseline and 14 weeks
blood samples measured: plasma CT pro endothelin-1, IgG, IgA, NT pro BNP, albumin, free protein
Baseline and 14 weeks
Change from baseline in SF36 questionnaire score at 14 weeks
Time Frame: Baseline and 14 weeks
SF36 quality of life interview
Baseline and 14 weeks
Change from baseline in feces alfa 1 antitrypsin at 14 weeks
Time Frame: Baseline and 14 weeks
Fecal alfa 1 antitrypsin in mg/g
Baseline and 14 weeks
Number of participants with adverse events
Time Frame: 2, 6, 10 and 14 weeks after start of treatment
general interview on adverse effects, and questions with special focus on typical adverse effects in Bosentan
2, 6, 10 and 14 weeks after start of treatment
Change from baseline in vital signs
Time Frame: Baseline, 2, 6, 10 and 14 weeks
Systemic bloodpressure in mmHg, Pulse in min-1, Oxygen saturation in percent
Baseline, 2, 6, 10 and 14 weeks
Change from baseline in control blood samples
Time Frame: Baseline, 2, 6, 10 and 14 weeks
Liver and renal biomarkers, Hb, PCV, trc and hCG for women
Baseline, 2, 6, 10 and 14 weeks
Change from baseline in cardiac output/pulmonary blood flow
Time Frame: Baseline and 14 weeks
CO measured by Stringer Wassermann method during ergometer bicycle test
Baseline and 14 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rigshospitalet, Denmark

Collaborators

Aarhus University Hospital
Bispebjerg Hospital
Actelion

Investigators

  • Study Director: Lars Sondergaard, DMSc, Rigshospitalet, Denmark
  • Principal Investigator: Anders H Hebert, MD, Rigshospitalet, Denmark

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2011

Primary Completion (Actual)

March 1, 2013

Study Completion (Actual)

March 1, 2013

Study Registration Dates

First Submitted

February 8, 2011

First Submitted That Met QC Criteria

February 8, 2011

First Posted (Estimate)

February 9, 2011

Study Record Updates

Last Update Posted (Estimate)

April 19, 2013

Last Update Submitted That Met QC Criteria

April 18, 2013

Last Verified

April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TEMPO study
  • 2010-022389-28 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Tricuspid Atresia

Clinical Trials on Bosentan

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Poland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe