Condition category
Respiratory
Date applied
22/03/2006
Date assigned
20/04/2006
Last edited
07/05/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Michael Tamm

ORCID ID

Contact details

University Hospital Basel
Petersgraben 4
Basel
4031
Switzerland
+41 (0)61 265 5184
stolzd@uhbs.ch

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

TOP Study

Study hypothesis

We hypothesise that the orally administered dual endothelin-receptor antagonist bosentan improves exercise capacity (as measured by the six-minute walk test, mobile spiroergometry) and pulmonary perfusion (as measured by computed tomography single photon emission computed tomography [CT SPECT]) and is well tolerated at a dose of 125 mg, twice daily, in patients with pulmonary hypertension due to severe chronic obstructive pulmonary disease (COPD)

Ethics approval

Approved by Ethics Committee of Basel (EKBB) on 20/03/2006, reference number: 317/05. This trial was also approved by the Swiss Federal Authority (Swiss Agency for Therapeutic Products [SWISSMEDIC]), protocol reference number: 2006 DR 2086.

Study design

Interventional, prospective, randomised, double-blind, placebo-controlled study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Chronic obstructive pulmonary disease

Intervention

Bosentan dose increases from 62.5 mg twice a day (BID) to 125 mg DIB after 14 days, if there is no increase in AST/ALT greater than 3 x normal values. If there is an increase of AST/ALT greater than 3 times but less than 5 times that of the normal values, the dosage is maintained at 62.5 mg BID. If the increase if greater than 5 times the normal value, therapy with bosentan has to be discontinued. The control group will receive a placebo.

Intervention type

Drug

Phase

Not Specified

Drug names

Bosentan

Primary outcome measures

Improvement in six feet walking distance after three months therapy.

Secondary outcome measures

Improvement or change after three months in regard to:
1. Partial pressure of Oxygen (pO2) measured in the Arterial Blood Gas Analysis (ABGA)
2. Maximal oxygen uptake (VO2 max), Saturation of Oxygen in arterial blood (SaO2) as measured by mobile exercise test
3. Perfusion pattern on the thorax SPECT-CT (SYMBIA T2), comparing different morphologic types of emphysema
4. Systolic pulmonary pressure, right-ventricular enlargement and right-ventricular ejection fraction as measured by echocardiography
5. Bodyplethysmography and Carbon Dioxide (CO2) diffusion capacity
6. Brain natriuretic peptide
7. Liver enzymes (AST, ALT)

Overall trial start date

01/04/2006

Overall trial end date

01/12/2006

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients with a diagnosis of severe (forced expiratory volume in one second [FEV1] less than 50%), or very severe (FEV1 less than 30%) COPD and/or severe emphysema (markedly impaired diffusion capacity), according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines will be included in the study. Post-bronchodilator lung function test will be appreciated, as suggested in the guidelines. Patients will be screened in regard to echocardiographical technical feasibility. Moreover, patients will undergo routine clinical, land laboratory evaluation as well as full lung function testing.
2. Greater than 18 years of age
3. Postmenopausal women or women with negative pre-treatment pregnancy test as well as a reliable method of contraception during study treatment and for at least three months after study treatment termination. Reliable methods of contraception are:
3.1. Barrier type devices (e.g. female condom, diaphragm, contraceptive sponge) only in combination with a spermicide
3.2. Intra-uterine devices
3.3. Oral, injectable or implantable contraceptives only in combination with a barrier method
3.4. Hormone-based contraceptives alone, regardless of the route of administration, are not considered as reliable methods of contraception
3.5. Abstention, rhythm method, and contraception by the partner alone are not acceptable methods of contraception

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

24

Participant exclusion criteria

1. Mental disorder preventing appropriate judgment concerning study participation
2. Significant comorbidity resulting in reduced life expectancy
3. Infectious or non-infections hepatitis
4. Known intolerance to bosentan
5. Significant exacerbation of COPD within the last month
6. Insufficient technical quality in the echocardiographic evaluation
7. Systolic Blood Pressure (BP) less than 85 mmHg
8. Body weight less than 40 kg
9. Hemoglobin concentration less than 75% of the lower limit of the normal range
10. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) values greater than 3 times the upper limit of normal
11. Moderate to severe hepatic impairment (Child-Pugh B or C)
12. Patients with decompensated and/or not corrected right heart failure
13. Concomitant treatment with:
13.1. Calcineurin-inhibitors (e.g. cyclosporine A and tacrolimus, everolimus, sirolimus)
13.2. CYP2C9 and CYP3A4 inhibitors (e.g. fluconazole, amiodarone, miconazole, ketoconazole, itraconazole, ritonavir, voriconazole, metronidazole)
13.3. Protease inhibitors (e.g. ritonavir) or glibenclamide (glyburide) within 1 week of randomisation

Recruitment start date

01/04/2006

Recruitment end date

01/12/2006

Locations

Countries of recruitment

Switzerland

Trial participating centre

University Hospital Basel
Basel
4031
Switzerland

Sponsor information

Organisation

University Hospital Basel (USB) (Switzerland)

Sponsor details

Division of Pneumology
Petersgraben 4
Basel
4031
Switzerland
+41 (0)61 265 5184
stolzd@uhbs.ch

Sponsor type

University/education

Website

http://www.unispital-basel.ch/

Funders

Funder type

University/education

Funder name

University Hospital Basel (USB) (Switzerland) - Department of Pneumology

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Results in http://www.ncbi.nlm.nih.gov/pubmed/18448495

Publication citations

  1. Results

    Stolz D, Rasch H, Linka A, Di Valentino M, Meyer A, Brutsche M, Tamm M, A randomised, controlled trial of bosentan in severe COPD., Eur. Respir. J., 2008, 32, 3, 619-628, doi: 10.1183/09031936.00011308.

Additional files

Editorial Notes