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

NCT01292551 | Completed Phase 2 DMC

• 2 other identifiers: TEMPO study2010-022389-28
• Study Type: interventional
• Target: 75
• Locations: 2 countries
• Sites: 4

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.

Conditions

Hypoplastic Left Heart Syndrome; Tricuspid Atresia; Other Specified Congenital Anomalies of Heart

Keywords

single ventricle physiology; Fontan procedure

Outcome Measures

Primary Outcomes (1)

• Change from baseline in VO2max at 14 weeks

  Maximal O2 uptake in ml/min/kg in ergometer bicycle test

  Baseline and 14 weeks

Secondary Outcomes (7)

• Change from baseline in blood samples at 14 weeks

  Baseline and 14 weeks

• Change from baseline in SF36 questionnaire score at 14 weeks

  Baseline and 14 weeks

• Change from baseline in feces alfa 1 antitrypsin at 14 weeks

  Baseline and 14 weeks

• Number of participants with adverse events

  2, 6, 10 and 14 weeks after start of treatment

• Change from baseline in vital signs

  Baseline, 2, 6, 10 and 14 weeks

Study Arms (2)

Bosentan

ACTIVE COMPARATOR

Drug: Bosentan

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Bosentan DRUG

tablets Bosentan 62,5 mg x 2 daily for two weeks, then 125 mg x 2 daily for 12 weeks

Also known as: Bosentan: Tracleer

Bosentan

Placebo DRUG

Placebo tablets 2 x daily for 2 weeks, then change to different placebo tablets to match Bosentan group, 2 x daily for 12 weeks

Placebo

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Aarhus University Hospital: collaborator
• Bispebjerg Hospital: collaborator
• Actelion: collaborator

Study Sites (4)

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Lund University Hospital

Lund, Sweden

Location

Karolinska Institutet

Stockholm, Sweden

Location

Related Publications (2)

• Hebert A, Mikkelsen UR, Thilen U, Idorn L, Jensen AS, Nagy E, Hanseus K, Sorensen KE, Sondergaard L. Bosentan improves exercise capacity in adolescents and adults after Fontan operation: the TEMPO (Treatment With Endothelin Receptor Antagonist in Fontan Patients, a Randomized, Placebo-Controlled, Double-Blind Study Measuring Peak Oxygen Consumption) study. Circulation. 2014 Dec 2;130(23):2021-30. doi: 10.1161/CIRCULATIONAHA.113.008441. Epub 2014 Oct 20.

  PMID: 25446057 DERIVED

• Hebert A, Jensen AS, Idorn L, Sorensen KE, Sondergaard L. The effect of bosentan on exercise capacity in Fontan patients; rationale and design for the TEMPO study. BMC Cardiovasc Disord. 2013 May 11;13:36. doi: 10.1186/1471-2261-13-36.

  PMID: 23663658 DERIVED

MeSH Terms

Conditions

Hypoplastic Left Heart Syndrome; Tricuspid Atresia

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heart Valve Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Lars Sondergaard, DMSc

  Rigshospitalet, Denmark

  STUDY DIRECTOR

• Anders H Hebert, MD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: February 8, 2011
• First Posted: February 9, 2011
• Study Start: February 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: April 19, 2013

Record last verified: 2013-04

Locations

DK (2); SE (2)