Pulmonary Arterial HypertensionEPICNCT02484807
Effect of Pharmacologic Interaction Between ERAs and PDE-5 Inhibitors on Medication Serum Levels and Clinical Disease Status in Patients With PAH
An observational study of Pulmonary Arterial Hypertension, run by Heidelberg University at 1 site in Germany.
Trial summary
The development of disease-targeted medication for the treatment of pulmonary arterial hypertension (PAH) has significantly improved within the last years, leading to the development of 10 approved agents. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension
- How many people
- 125 participants
- Where
- 1 siteGermany
- Study dates
- May 2015to Dec 2016
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: patients with pulmonary arterial hypertension receiving disease-targeted combination therapy
Who may be able to join
- Men and women ≥ 18 years old
- Diagnosis of PAH according to ESC/ERS-guidelines: patients with manifest pulmonary arterial hypertension, mean pulmonary arterial pressure ≥25mmHg, measured by right heart catheterization.
- Combination treatment with ERA (Bosentan, Ambrisentan or Macitentan) and PDE-5-Inhibitor (Sildenafil or Tadalafil) for more than 3 months.
Who cannot join
- Underage patients
- Pregnancy or lactation
Trial locations and contacts
1 site in 1 country.
Germany1 site
Centre for pulmonary hypertension, Thoraxclinic at the University Hospital Heidelberg
Heidelberg, 69126
About this study
Official title: Effect of Pharmacologic Interaction Between Endothelin-Receptor-Antagonists and Phosphodiesterase-5 Inhibitors on Medication Serum Levels and Clinical Disease Status in Patients Wih Pulmonary Arterial Hypertension
The development of disease-targeted medication for the treatment of pulmonary arterial hypertension (PAH) has significantly improved within the last years, leading to the development of 10 approved agents. Combination treatment with Endothelin-Receptor-Antagonists (ERA) and Phosphodiesterase-Type-5-Inibitors (PDE-5-Inhibitor) has become increasingly important for the treatment of PAH. In a recent press release, the results of the AMBITION study reported that an upfront combination treatment immediately after diagnosis leads to a delayed disease progression [4]. Thus, the question if there is a clinically relevant pharmaco-dynamic drug-drug interaction is of rising interest.
Read the detailed description
Mechanisms of action Three ERAs have been approved for the treatment of PAH including the dual inhibitors Bosentan and Macitentan and the selective Endothelin Receptor type A inhibitor (ETA-Inhibitor) Ambrisentan. The dual antagonists inhibit both ETA- and the type B (ETB)-receptor, while the selective antagonist only affects the ETA-receptor [2]. The physiologic ligand of the receptors is Endothelin-1, which binds to the ETA-receptor and causes vasoconstriction and proliferation of the vascular smooth muscle cells. The binding to the ETB-receptor leads to an endogenous production of NO and prostacyclin in the endothelial cells.
PDE-5-Inhibitors include the two substances Sildenafil and Tadalafil. They inhibit the degradation of cyclic guanosine monophosphate (cGMPs), which triggers the vasodilative effect of endothelial NO.
Interaction There is evidence for the pharmacokinetic interaction (inhibition / induction of critical targets of drug metabolism and drug distribution) of both substance classes: the PDE-5-Inhibitors Sildenafil and Tadalafil are mainly eliminated in the liver by the hepatic enzyme Cytochrom-P450-Oxygenase type 3A4 (CYP3A4). The dual inhibitor Bosentan is both a substrate and an inductor of the Cytochrom-P450-Oxydase type 3A4 and type 2C9 [5,6].
It has already been shown in an in vivo-study, that simultaneous application of PDE-5-Inhibitors and Bosentan leads to a systemic reduction of the PDE-5-Inhibitor concentration of 40%, due to the CYP3A4-inducing effect of Bosentan [5]. Sildenafil, in contrast, leads to a decreased degradation of Bosentan in the liver with an approximately 50% increase in plasma leves. An anticipated result, especially when higher dosages of Sildenafil are applied, is the accumulation of Bosentan and reduction of Sildenafil levels.
A recent in vitro-study has shown that Tadalafil may also serve as CYP3A4-inductor, while this effect has not been detected for Sildenafil [7].
In contrast Macitentan which has been approved in 2013, has no clinically relevant CYP3A4-inducing effects. [8]. The in vitro-study has also detected a further interaction between ERAs and PDE-5-Inhibitors. Both PDE-5-Inhibitors Sildenafil and Tadalafil affect the transport molecules organic anion transporting polypeptides (OATPs), which are responsible for the hepatocellular intake of the dual ERA Bosentan. They also had a mild effect on the intake of Ambrisentan.
Sildenafil is a potent inhibitor of OATPs, whereas Tadalafil shows only minor inhibition of OATPs [7]. Both Sildenafil and Tadalafil significantly reduce the intracellular concentration of Bosentan in the liver, leading to a reduced degradation of Bosentan. For Ambrisentan this effect seemed to be less pronounced [7]. Consequently, this mechanisms of action lead to higher ERA-levels and to decreased PDE-5-Inhibitor plasma concentrations in patients receiving combination treatment. The most distinct interaction is expected for the combination of Sildenafil (PDE-5-Inhibitor) and Bosentan (ERA).
Up to now, the prevalence and role of this pharmacokinetic interaction for the clinical status and progression of the disease is not clear. Respective combination treatments have only been investigated in healthy male volunteers so far [5,9].
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- no intervention, only observation of different groups
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
no intervention, only observation of different groupsOther
| Study group | Role | What they receive |
|---|---|---|
| Bosentan + Sildenafil | Combination treatment with Bosentan + Sildenafil at baseline Receives: Other: no intervention, only observation of different groups | |
| Bosentan + Tadalafil | Combination treatment with Bosentan + Tadalafil at baseline Receives: Other: no intervention, only observation of different groups | |
| Ambrisentan + Sildenafil | Combination treatment with Ambrisentan + Sildenafil at baseline Receives: Other: no intervention, only observation of different groups | |
| Ambrisentan + Tadalafil | Combination treatment with Ambrisentan + Tadalafil at baseline Receives: Other: no intervention, only observation of different groups | |
| Macitentan + Sildenafil | Combination treatment with Macitentan + Sildenafil at baseline Receives: Other: no intervention, only observation of different groups | |
| Macitentan + Tadalafil | Combination treatment with Macitentan + Tadalafil at baseline Receives: Other: no intervention, only observation of different groups |
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterisation of Medication Levels
comparison of different combination treatment arms (mean ± standard deviation), measurement of endothelin receptor antagonist plasma concentrations and PDE-5I plasma concentrations, results given es multiple of the expected mean plasma concentration (MOM). Due to technical setup measurement of plasma concentrations of macitentan was not possible.
The expected mean concentration ranges (MOM) refer to data extracted from published plasma concentration-time profiles measured during monotherapy with sildenafil, tadalafil, bosentan, and ambrisentan and served as comparative values. Each individually measured drug concentration was set in proportion to the expected mean concentration and expressed as a multiple of the expected mean (MoM), with values <1 denoting lower and values >1 higher values than the expected mean.
Measured: baseline vs. measurement after 3-6 months
Secondary outcomes (6)
Impact of Medication Adjustment
Change of medication serum levels after clinically indicated medication adaptation in patients who received Bosentan + Sildenafil in the beginning and changed the ERA to Macitentan
- change of mean levels ± standard deviation
- frequency of borderline medication serum levels or medication levels out of the therapeutic window The expected mean concentration ranges (MOM) refer to data extracted from published plasma concentration-time profiles measured during monotherapy with sildenafil, tadalafil, bosentan, and ambrisentan and served as comparative values. Each individually measured drug concentration was set in proportion to the expected mean concentration and expressed as a multiple of the expected mean (MoM), with values <1 denoting lower and values >1 higher values than the expected mean.
Measured: baseline vs. measurement 3-6 months after switch
Clinical Relevance 6 Minute Walking Distance
- Changes of medication levels after adjustment of combination therapy if clinically indicated
- correlation with clinical routine parameters indicating clinical disease status
Measured: baseline vs. measurement 3-6 months after switch
Clinical Relevance NTproBNP
- Changes of medication levels after adjustment of combination therapy if clinically indicated
- correlation with clinical routine parameters indicating clinical disease status
Measured: baseline vs. measurement after 3-6 months
Clinical Relevance Echocardiography Systolic Pulmonary Arterial Pressure (sPAP)
- Changes of medication levels after adjustment of combination therapy if clinically indicated
- correlation with clinical routine parameters indicating clinical disease status
Measured: baseline vs. measurement after 3-6 months
Clinical Relevance Echocardiography Tricuspid Annular Plane Systolic Excursion (TAPSE)
- Changes of medication levels after adjustment of combination therapy if clinically indicated
- correlation with clinical routine parameters indicating clinical disease status
Measured: baseline vs. measurement after 3-6 months
Clinical Relevance Blood Gas Analysis Oxygen Saturation
- Changes of medication levels after adjustment of combination therapy if clinically indicated
- correlation with clinical routine parameters indicating clinical disease status
Measured: baseline vs. measurement after 3-6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2015 (estimated)
- Study startMay 2015
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 125 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heidelberg University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Dr. med. Ekkehard Gruenig, Heidelberg University
- Investigators
- Ekkehard Grünig, MD, Principal investigator, Thoraxclinic at the University Hospital Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02484807
- Sponsor's protocol ID
- EPIC-01
- Acronym
- EPIC
- Status last verified
- Jan 2020
- First submitted
- 24 Jun 2015
- Last updated
- 5 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau G; ESC Committee for Practice Guidelines (CPG). Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J. 2009 Oct;30(20):2493-537. doi: 10.1093/eurheartj/ehp297. Epub 2009 Aug 27. No abstract available.
PubMed 19713419Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004 Sep 30;351(14):1425-36. doi: 10.1056/NEJMra040291. No abstract available.
PubMed 15459304Voelkel NF, Gomez-Arroyo J, Abbate A, Bogaard HJ, Nicolls MR. Pathobiology of pulmonary arterial hypertension and right ventricular failure. Eur Respir J. 2012 Dec;40(6):1555-65. doi: 10.1183/09031936.00046612. Epub 2012 Jun 27.
PubMed 22743666Wrishko RE, Dingemanse J, Yu A, Darstein C, Phillips DL, Mitchell MI. Pharmacokinetic interaction between tadalafil and bosentan in healthy male subjects. J Clin Pharmacol. 2008 May;48(5):610-8. doi: 10.1177/0091270008315315. Epub 2008 Feb 27.
PubMed 18305126Paul GA, Gibbs JS, Boobis AR, Abbas A, Wilkins MR. Bosentan decreases the plasma concentration of sildenafil when coprescribed in pulmonary hypertension. Br J Clin Pharmacol. 2005 Jul;60(1):107-12. doi: 10.1111/j.1365-2125.2005.02383.x.
PubMed 15963102Weiss J, Theile D, Spalwisz A, Burhenne J, Riedel KD, Haefeli WE. Influence of sildenafil and tadalafil on the enzyme- and transporter-inducing effects of bosentan and ambrisentan in LS180 cells. Biochem Pharmacol. 2013 Jan 15;85(2):265-73. doi: 10.1016/j.bcp.2012.11.020. Epub 2012 Dec 5.
PubMed 23219525Weiss J, Theile D, Ruppell MA, Speck T, Spalwisz A, Haefeli WE. Interaction profile of macitentan, a new non-selective endothelin-1 receptor antagonist, in vitro. Eur J Pharmacol. 2013 Feb 15;701(1-3):168-75. doi: 10.1016/j.ejphar.2013.01.010. Epub 2013 Jan 23.
PubMed 23353592Burgess G, Hoogkamer H, Collings L, Dingemanse J. Mutual pharmacokinetic interactions between steady-state bosentan and sildenafil. Eur J Clin Pharmacol. 2008 Jan;64(1):43-50. doi: 10.1007/s00228-007-0408-z. Epub 2007 Nov 27.
PubMed 18040672
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Pharmacologic Interaction Between Endothelin-Receptor-Antagonists and Phosphodiesterase-5 Inhibitors on Medication Serum Levels and Clinical Disease Status in Patients Wih Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT02484807
- Acronym / sponsor ID
- EPIC / EPIC-01
- Conditions
- Pulmonary Arterial Hypertension
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 125 participants (actual)
- Lead sponsor
- Heidelberg UniversityUniversity, hospital or other
- Study start
- May 2015 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 30 Jun 2015 (estimated)
- Results
- Posted 5 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The development of disease-targeted medication for the treatment of pulmonary arterial hypertension (PAH) has significantly improved within the last years, leading to the development of 10 approved agents. Combination treatment with Endothelin-Receptor-Antagonists (ERA) and Phosphodiesterase-Type-5-Inibitors (PDE-5-Inhibitor) has become increasingly important for the treatment of PAH. In a recent press release, the results of the AMBITION study reported that an upfront combination treatment immediately after diagnosis leads to a delayed disease progression [4]. Thus, the question if there is a clinically relevant pharmaco-dynamic drug-drug interaction is of rising interest.
Detailed description
Mechanisms of action Three ERAs have been approved for the treatment of PAH including the dual inhibitors Bosentan and Macitentan and the selective Endothelin Receptor type A inhibitor (ETA-Inhibitor) Ambrisentan. The dual antagonists inhibit both ETA- and the type B (ETB)-receptor, while the selective antagonist only affects the ETA-receptor [2]. The physiologic ligand of the receptors is Endothelin-1, which binds to the ETA-receptor and causes vasoconstriction and proliferation of the vascular smooth muscle cells. The binding to the ETB-receptor leads to an endogenous production of NO and prostacyclin in the endothelial cells.
PDE-5-Inhibitors include the two substances Sildenafil and Tadalafil. They inhibit the degradation of cyclic guanosine monophosphate (cGMPs), which triggers the vasodilative effect of endothelial NO.
Interaction There is evidence for the pharmacokinetic interaction (inhibition / induction of critical targets of drug metabolism and drug distribution) of both substance classes: the PDE-5-Inhibitors Sildenafil and Tadalafil are mainly eliminated in the liver by the hepatic enzyme Cytochrom-P450-Oxygenase type 3A4 (CYP3A4). The dual inhibitor Bosentan is both a substrate and an inductor of the Cytochrom-P450-Oxydase type 3A4 and type 2C9 [5,6].
It has already been shown in an in vivo-study, that simultaneous application of PDE-5-Inhibitors and Bosentan leads to a systemic reduction of the PDE-5-Inhibitor concentration of 40%, due to the CYP3A4-inducing effect of Bosentan [5]. Sildenafil, in contrast, leads to a decreased degradation of Bosentan in the liver with an approximately 50% increase in plasma leves. An anticipated result, especially when higher dosages of Sildenafil are applied, is the accumulation of Bosentan and reduction of Sildenafil levels.
A recent in vitro-study has shown that Tadalafil may also serve as CYP3A4-inductor, while this effect has not been detected for Sildenafil [7].
In contrast Macitentan which has been approved in 2013, has no clinically relevant CYP3A4-inducing effects. [8]. The in vitro-study has also detected a further interaction between ERAs and PDE-5-Inhibitors. Both PDE-5-Inhibitors Sildenafil and Tadalafil affect the transport molecules organic anion transporting polypeptides (OATPs), which are responsible for the hepatocellular intake of the dual ERA Bosentan. They also had a mild effect on the intake of Ambrisentan.
Sildenafil is a potent inhibitor of OATPs, whereas Tadalafil shows only minor inhibition of OATPs [7]. Both Sildenafil and Tadalafil significantly reduce the intracellular concentration of Bosentan in the liver, leading to a reduced degradation of Bosentan. For Ambrisentan this effect seemed to be less pronounced [7]. Consequently, this mechanisms of action lead to higher ERA-levels and to decreased PDE-5-Inhibitor plasma concentrations in patients receiving combination treatment. The most distinct interaction is expected for the combination of Sildenafil (PDE-5-Inhibitor) and Bosentan (ERA).
Up to now, the prevalence and role of this pharmacokinetic interaction for the clinical status and progression of the disease is not clear. Respective combination treatments have only been investigated in healthy male volunteers so far [5,9].
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Bosentan + Sildenafil | – | Other: no intervention, only observation of different groupsCombination treatment with Bosentan + Sildenafil at baseline |
| Bosentan + Tadalafil | – | Other: no intervention, only observation of different groupsCombination treatment with Bosentan + Tadalafil at baseline |
| Ambrisentan + Sildenafil | – | Other: no intervention, only observation of different groupsCombination treatment with Ambrisentan + Sildenafil at baseline |
| Ambrisentan + Tadalafil | – | Other: no intervention, only observation of different groupsCombination treatment with Ambrisentan + Tadalafil at baseline |
| Macitentan + Sildenafil | – | Other: no intervention, only observation of different groupsCombination treatment with Macitentan + Sildenafil at baseline |
| Macitentan + Tadalafil | – | Other: no intervention, only observation of different groupsCombination treatment with Macitentan + Tadalafil at baseline |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients with pulmonary arterial hypertension receiving disease-targeted combination therapy
Key inclusion criteria (3 listed)
- Men and women ≥ 18 years old
- Diagnosis of PAH according to ESC/ERS-guidelines: patients with manifest pulmonary arterial hypertension, mean pulmonary arterial pressure ≥25mmHg, measured by right heart catheterization.
- Combination treatment with ERA (Bosentan, Ambrisentan or Macitentan) and PDE-5-Inhibitor (Sildenafil or Tadalafil) for more than 3 months.
Key exclusion criteria (2 listed)
- Underage patients
- Pregnancy or lactation
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 |
|---|---|---|
| no intervention, only observation of different groups | Other | Ambrisentan + Sildenafil, Ambrisentan + Tadalafil, Bosentan + Sildenafil, Bosentan + Tadalafil, Macitentan + Sildenafil, Macitentan + Tadalafil |
Primary outcome
Characterisation of Medication Levels
Time frame: baseline vs. measurement after 3-6 months
comparison of different combination treatment arms (mean ± standard deviation), measurement of endothelin receptor antagonist plasma concentrations and PDE-5I plasma concentrations, results given es multiple of the expected mean plasma concentration (MOM). Due to technical setup measurement of plasma concentrations of macitentan was not possible. The expected mean concentration ranges (MOM) refer to data extracted from published plasma concentration-time profiles measured during monotherapy with sildenafil, tadalafil, bosentan, and ambrisentan and served as comparative values. Each individually measured drug concentration was set in proportion to the expected mean concentration and expressed as a multiple of the expected mean (MoM), with values <1 denoting lower and values >1 higher values than the expected mean.
6 secondary outcomes
Impact of Medication Adjustment
Time frame: baseline vs. measurement 3-6 months after switch
Clinical Relevance 6 Minute Walking Distance
Time frame: baseline vs. measurement 3-6 months after switch
Clinical Relevance NTproBNP
Time frame: baseline vs. measurement after 3-6 months
Clinical Relevance Echocardiography Systolic Pulmonary Arterial Pressure (sPAP)
Time frame: baseline vs. measurement after 3-6 months
Clinical Relevance Echocardiography Tricuspid Annular Plane Systolic Excursion (TAPSE)
Time frame: baseline vs. measurement after 3-6 months
Clinical Relevance Blood Gas Analysis Oxygen Saturation
Time frame: baseline vs. measurement after 3-6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19713419Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau G; ESC Committee for Practice Guidelines (CPG). Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J. 2009 Oct;30(20):2493-537. doi: 10.1093/eurheartj/ehp297. Epub 2009 Aug 27. No abstract available.
- Background: PubMed 15459304Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004 Sep 30;351(14):1425-36. doi: 10.1056/NEJMra040291. No abstract available.
- Background: PubMed 22743666Voelkel NF, Gomez-Arroyo J, Abbate A, Bogaard HJ, Nicolls MR. Pathobiology of pulmonary arterial hypertension and right ventricular failure. Eur Respir J. 2012 Dec;40(6):1555-65. doi: 10.1183/09031936.00046612. Epub 2012 Jun 27.
- Background: PubMed 18305126Wrishko RE, Dingemanse J, Yu A, Darstein C, Phillips DL, Mitchell MI. Pharmacokinetic interaction between tadalafil and bosentan in healthy male subjects. J Clin Pharmacol. 2008 May;48(5):610-8. doi: 10.1177/0091270008315315. Epub 2008 Feb 27.
- Background: PubMed 15963102Paul GA, Gibbs JS, Boobis AR, Abbas A, Wilkins MR. Bosentan decreases the plasma concentration of sildenafil when coprescribed in pulmonary hypertension. Br J Clin Pharmacol. 2005 Jul;60(1):107-12. doi: 10.1111/j.1365-2125.2005.02383.x.
- Background: PubMed 23219525Weiss J, Theile D, Spalwisz A, Burhenne J, Riedel KD, Haefeli WE. Influence of sildenafil and tadalafil on the enzyme- and transporter-inducing effects of bosentan and ambrisentan in LS180 cells. Biochem Pharmacol. 2013 Jan 15;85(2):265-73. doi: 10.1016/j.bcp.2012.11.020. Epub 2012 Dec 5.
- Background: PubMed 23353592Weiss J, Theile D, Ruppell MA, Speck T, Spalwisz A, Haefeli WE. Interaction profile of macitentan, a new non-selective endothelin-1 receptor antagonist, in vitro. Eur J Pharmacol. 2013 Feb 15;701(1-3):168-75. doi: 10.1016/j.ejphar.2013.01.010. Epub 2013 Jan 23.
- Background: PubMed 18040672Burgess G, Hoogkamer H, Collings L, Dingemanse J. Mutual pharmacokinetic interactions between steady-state bosentan and sildenafil. Eur J Clin Pharmacol. 2008 Jan;64(1):43-50. doi: 10.1007/s00228-007-0408-z. Epub 2007 Nov 27.
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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.
Ekkehard Grünig, MD principal investigator
Thoraxclinic at the University Hospital Heidelberg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pulmonary Arterial Hypertension, run by Heidelberg University at 1 site in Germany.
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 3 inclusion and 2 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 5 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Characterisation of Medication Levels (time frame: baseline vs. measurement after 3-6 months). 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 NCT02484807, which also lists 8 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 5 Feb 2020.