Hypoplastic Left Heart SyndromePhase 2TEMPONCT01292551
Study of Placebo or Bosentan to Treat Patients With Single Ventricle Physiology.
A Phase 2 study testing Bosentan in people with Hypoplastic Left Heart Syndrome and Tricuspid Atresia, run by Copenhagen University Hospital, Rigshospitalet at 4 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Hypoplastic Left Heart Syndrome, Tricuspid Atresia, Other Specified Congenital Anomalies of Heart
- What is being tested?
- Bosentan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Feb 2011to Mar 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Denmark2 sites
Aarhus University Hospital
Aarhus, 8200
Rigshospitalet
Copenhagen, 2100
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Hypoplastic Left Heart Syndrome, Tricuspid Atresia, Other Specified Congenital Anomalies of Heart
- Being tested
- Bosentan, Placebo
- Keywords
- single ventricle physiology, Fontan procedure
- Medical subject headings
- Hypoplastic Left Heart Syndrome, Tricuspid Atresia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosentanDrug
Also called Bosentan: Tracleer
tablets Bosentan 62,5 mg x 2 daily for two weeks, then 125 mg x 2 daily for 12 weeks
PlaceboDrug
Placebo tablets 2 x daily for 2 weeks, then change to different placebo tablets to match Bosentan group, 2 x daily for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Bosentan | Active comparator | Not described Receives: Drug: Bosentan |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in VO2max at 14 weeks
Maximal O2 uptake in ml/min/kg in ergometer bicycle test
Measured: Baseline and 14 weeks
Secondary outcomes (7)
Change from baseline in blood samples at 14 weeks
blood samples measured: plasma CT pro endothelin-1, IgG, IgA, NT pro BNP, albumin, free protein
Measured: Baseline and 14 weeks
Change from baseline in SF36 questionnaire score at 14 weeks
SF36 quality of life interview
Measured: Baseline and 14 weeks
Change from baseline in feces alfa 1 antitrypsin at 14 weeks
Fecal alfa 1 antitrypsin in mg/g
Measured: Baseline and 14 weeks
Number of participants with adverse events
general interview on adverse effects, and questions with special focus on typical adverse effects in Bosentan
Measured: 2, 6, 10 and 14 weeks after start of treatment
Change from baseline in vital signs
Systemic bloodpressure in mmHg, Pulse in min-1, Oxygen saturation in percent
Measured: Baseline, 2, 6, 10 and 14 weeks
Change from baseline in control blood samples
Liver and renal biomarkers, Hb, PCV, trc and hCG for women
Measured: Baseline, 2, 6, 10 and 14 weeks
Change from baseline in cardiac output/pulmonary blood flow
CO measured by Stringer Wassermann method during ergometer bicycle test
Measured: Baseline and 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2011 (estimated)
- Study startFeb 2011
- Primary completionMar 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hypoplastic Left Heart SyndromeStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital, Bispebjerg Hospital, Actelion
- Responsible party
- Principal investigator, Anders Hebert, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Lars Sondergaard, DMSc, Study director, Copenhagen University Hospital, RigshospitaletAnders H Hebert, MD, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01292551
- Sponsor's protocol ID
- TEMPO study
- Other IDs
- 2010-022389-28
- Acronym
- TEMPO
- Status last verified
- Apr 2013
- First submitted
- 8 Feb 2011
- Last updated
- 19 Apr 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 25446057Hebert 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.
PubMed 23663658
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment With Endothelin Antagonist to Tcpc Patients; a Multicenter, Randomized, Prospective Study Measuring Maximal O2 Uptake in Ergometer Bicycle Test
- ClinicalTrials.gov ID
- NCT01292551
- Acronym / sponsor ID
- TEMPO / TEMPO study
- Conditions
- Hypoplastic Left Heart Syndrome, Tricuspid Atresia, Other Specified Congenital Anomalies of Heart
- Keywords
- single ventricle physiology, Fontan procedure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- Aarhus University Hospital, Bispebjerg Hospital, Actelion
- Study start
- Feb 2011
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 9 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bosentan | Active comparator | Drug: Bosentan |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BosentanAlso: Bosentan: Tracleertablets Bosentan 62,5 mg x 2 daily for two weeks, then 125 mg x 2 daily for 12 weeks | Drug | Bosentan |
| PlaceboPlacebo tablets 2 x daily for 2 weeks, then change to different placebo tablets to match Bosentan group, 2 x daily for 12 weeks | Drug | Placebo |
Primary outcome
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
7 secondary outcomes
Change from baseline in blood samples at 14 weeks
Time frame: Baseline and 14 weeks
Change from baseline in SF36 questionnaire score at 14 weeks
Time frame: Baseline and 14 weeks
Change from baseline in feces alfa 1 antitrypsin at 14 weeks
Time frame: Baseline and 14 weeks
Number of participants with adverse events
Time frame: 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
Change from baseline in control blood samples
Time frame: Baseline, 2, 6, 10 and 14 weeks
Change from baseline in cardiac output/pulmonary blood flow
Time frame: Baseline and 14 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2013.
- Derived from this study: PubMed 25446057Hebert 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.
- Derived from this study: PubMed 23663658Hebert 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lars Sondergaard, DMSc study director
Copenhagen University Hospital, Rigshospitalet
Anders H Hebert, MD principal investigator
Copenhagen University Hospital, Rigshospitalet
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bosentan in people with Hypoplastic Left Heart Syndrome and Tricuspid Atresia, run by Copenhagen University Hospital, Rigshospitalet at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Denmark, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in VO2max at 14 weeks (time frame: Baseline and 14 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01292551, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2013.