Pulmonary HypertensionPhase 4NCT03835676
Effects of Treprostinil on Right Ventricular Structure and Function in Patients With Pulmonary Arterial Hypertension
A Phase 4 study testing Treprostinil in people with Pulmonary Hypertension, run by Magdi H. Yacoub at 1 site in Egypt.
Trial summary
In a group of patients with PAH treated with treprostinil, the current study aims to investigate the effect of treatment on RV structure and function; and correlate changes in RV structure and function with: World Health Organisation (WHO) class, Six-minute walk test, Quality of life (QoL), and Pre-specified… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Hypertension
- What is being tested?
- Treprostinil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteEgypt
- Study dates
- 1 May 2019to 1 Dec 2025
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PAH defined as a mean pulmonary artery pressure >25 mmHg on right heart catheterization at rest in the setting of a normal pulmonary arterial wedge pressure ≤15 mm Hg
- PAH that is idiopathic, familial, or associated with connective tissue disease.
- WHO class III or class IV despite the use of Endothelin receptor antagonists (ERA) and/or phosphodiesterase-5 inhibitors
- Age > 18 years
- Sinus rhythm
Who cannot join
- Patients with PAH associated with HIV infection, portal hypertension, congenital heart disease, schistosomiasis, chronic haemolytic anaemia
- Patients with pulmonary hypertension due to veno-occlusive disease and/or pulmonarycapillary haemangiomatosis, thromboembolism.
- Patients with left side heart disease that may contribute to pulmonary hypertension. Those patients are identified by having pulmonary wedge pressure >15 mmHg or elevated Left Ventricle (LV) end-diastolic pressure
- Patients who are severely disabled and will not be able to complete the study
- Patients with significant lung disease as shown by forced vital capacity (FVC) < 70% predicted, or forced expiratory volume at one second (FEV1)/FVC < 50% - Life expectancy <1 year due to severe PAH or any other forms of terminal disease.
- Pregnant women
- Refusal to give informed consent.
Trial locations and contacts
1 site in 1 country.
Egypt1 site, 1 recruiting
- Recruiting
Aswan Heart Centre - Magdi Yacoub Heart Foundation
Aswān
Ahmed M ElGuindy, MD, MRCP, +201001615151, ahmed_elguindy@hotmail.com
Shehab M Anwer, MD, +41788816333, shehabanwer@gmail.com
About this study
In a group of patients with PAH treated with treprostinil, the current study aims to investigate the effect of treatment on RV structure and function; and correlate changes in RV structure and function with: World Health Organisation (WHO) class, Six-minute walk test, Quality of life (QoL), and Pre-specified biomarkers (N-terminal B-type natriuretic peptide (NT-ProBNP), Tissue growth factor-B B-type natriuretic peptide BNP, and Profibrotic markers)
Read the detailed description
- Right ventricle (RV) in pulmonary hypertension
RV failure is the main cause of death in patients with pulmonary arterial hypertension (PAH), and the ability of the RV to adapt to the progressive increase in pulmonary vascular resistance associated with changes to the pulmonary vasculature in PAH is the main determinant of a patient's functional capacity and survival.
The response of the right ventricle (RV) to the increase in afterload produced by the pulmonary vascular changes characteristic of PAH is the key factor in the development of symptoms and in determining survival. Structurally, rising systolic and diastolic ventricular pressures increase diastolic and systolic stretch on the RV wall, which leads initially to an increase in muscle mass (adaptive hypertrophy) due to increased protein synthesis and an increase in cardiomyocyte size through the addition of sarcomeres. However, the RV cannot maintain adaptive hypertrophy in the face of sustained pressure overload, and eventually there is a transition to dilatation. At this stage there is no further increase, or even a decrease, in RV contractility, despite a further increase in load. One consequence of RV dilatation is an increase in wall tension, which increases myocardial oxygen demand and simultaneously decreases RV perfusion, leading to further compromised contractility and dilatation.
The exact mechanisms leading to the development of RV failure in patients with PAH are still unclear. Several mechanisms have been hypothesized: RV myocardial ischaemia, microvascular endothelial cell dysfunction, and myocyte apoptosis. In severe end-stage PAH, the RV changes its shape from the normal conformation to a more spherical one, and RV wall stress increases because RV wall thickness does not increase proportionally.
Given the importance of the RV in PAH, preservation and improvement of its function should be important aspects of therapy; however, there are currently few data specifically related to this aspect of treatment response.
- Vasodilator therapy and RV in pulmonary hypertension Although RV failure is the main cause of death in patients with pulmonary arterial hypertension (PAH), there is insufficient data about the effects of PAH treatment on RV geometry and function mainly because the RV assessment has been hampered by its complex crescentic shape, large infundibulum, and its trabecular nature. . This is specifically true for vasodilator therapies. Such therapies may affect the RV via direct cardiac-specific effects or indirect effects by reducing RV load. In a meta-analysis of clinical studies of PAH-specific therapies, active treatment was associated with a reduction in pulmonary vascular resistance which was accompanied by a decrease in pulmonary artery pressure, and an increase in stroke volume, but without an increase in contractility, suggesting that current PAH therapies have predominantly pulmonary vasodilating effects and have limited cardiac-specific effects. In a study of epoprostenol therapy, beneficial effects on RV structure and function (RV dilatation, curvature of the interventricular septum and maximal tricuspid regurgitant jet velocity) compared with placebo were reported following 12 weeks of treatment, with change in 6-min walk distance between baseline and 12 weeks being inversely related to the change in diastolic eccentricity index and pericardial effusion size. Such improvements may contribute to the clinical improvement and prolonged survival observed with epoprostenol in other studies.
Other evidence of improvements in RV parameters has come from descriptive studies using a number of PAH-specific therapies; however, these generally include a small number of patients, and this, together with the fact that such studies evaluated different parameters (both in terms of functional parameters and measures of RV size/mass), makes the assessment of results difficult. longer term studies of epoprostenol have not shown a positive treatment effect on RV size/mass although without a comparator arm it is not possible to determine whether long-term therapy slowed down the rate of RV hypertrophy or dilatation.
Overall, therefore, the effects of PAH-specific therapies on RV function remain to be fully investigated.
- Treprostinil Treprostinil is a tricyclic benzindene analogue of prostacyclin, and has as such similar anti-platelet and vasodilatory actions, including acute pulmonary vasodilation.
Treprostinil, a stable prostacyclin analog, has similar pharmacologic effects to epoprostenol, However, in contrast to epoprostenol, treprostinil is chemically stable at room temperature and neutral 'power of hydrogen' (pH) and has a longer half-life (elimination half-life of 4.5 h with distribution half-life of 40 min, compared with 2 to 3 min for epoprostenol) permitting continuous subcutaneous infusion (16). Treprostinil has been shown in a large multicenter randomized controlled trial to improve exercise capacity, clinical state, functional class, pulmonary hemodynamics, and quality of life in patients with pulmonary arterial hypertension.
- Assessment of RV with cardiac magnetic resonance imaging Currently, the most widely used noninvasive techniques are echocardiography and cardiac magnetic resonance imaging), and a number of potential indicators assessed using these methods have been proposed. Cardiac magnetic resonance imaging provides a higher spatial resolution, and is not limited by factors affecting echocardiography (e.g. acoustic window). Cardiac magnetic resonance imaging allows for the visualisation and measurement of complex three-dimensional geometry and it is therefore particularly suited to the complex morphology of the RV. Precise, noninvasive assessment of cardiac volumes and function is possible, without the need for geometric approximations, while assessments such as flow measurements in the heart and great vessels using techniques such as cine phase-contrast provide more comprehensive data on cardiac function than echocardiography.
- Conditions
- Pulmonary Hypertension
- Being tested
- Treprostinil
- Keywords
- Pulmonary hypertension, Right ventricular function
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TreprostinilDrug
Also called Remodulin
After inclusion and baseline measurements, patients will receive treprostinil in addition to background therapy for 24 months. Follow-up assessment will include:
- Clinical, echocardiographic, laboratory assessments will be repeated at 1, 3, 6, 12, 18, and 24 month (or when there is clinical indication)
- CMR will be performed at 6 monthly intervals for 2 years.
- Peak power output at 6,12, 18 and 24 month
- Right-side cardiac catheterization will be performed at 6, 12 , 18 and 24 months (or when there is clinical indication)
| Study group | Role | What they receive |
|---|---|---|
| Pulmonary hypertension treated with Treprostinil | Experimental | Thirty patients who will be treated with Treprostinil. Receives: Drug: Treprostinil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of Treprostinil effects on right ventricular structure and function using echocardiography
Assessment of RV structure and function by echocardiography
Measured: through study completion, an average of 5 years
Assessment of Treprostinil effects on right ventricular structure and function using Cardiac Magnetic Resonance Imaging (CMR).
Assessment of RV structure and function by cardiac magnetic resonance imaging (CMR).
Measured: through study completion, an average of 5 years
Secondary outcomes (4)
Correlate changes in RV structure and function with World Health Organisation (WHO) Class.
correlate changes in RV structure and function with the WHO class.
Measured: through study completion, an average of 5 years
Correlate changes in RV structure and function with the Six-minute walk test results
correlate changes in RV structure and function with the Six-minute walk test results
Measured: through study completion, an average of 5 years
Correlate changes in RV structure and function with QoL
correlate changes in RV structure and function with the Quality of life (QoL)
Measured: through study completion, an average of 5 years
Correlate changes in RV structure and function with prespecified biomarkers
correlate changes in RV structure and function with the Pre-specified biomarkers (NT-ProBNP, Tissue growth factor-B BNP, and Profibrotic markers)
Measured: through study completion, an average of 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2019
- Study start1 May 2019
- Primary completion1 Jun 2025 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Pulmonary 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- In a group of patients with PAH treated with treprostinil, the current study aims to investigate the effect of treatment on RV structure and function; and correlate changes in RV structure and function with: WHO class, Six-minute walk test, Quality of life (QoL), and Pre-specified biomarkers (NT-ProBNP, Tissue growth factor-B BNP, and Profibrotic markers)
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Magdi H. Yacoub
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Magdi H. Yacoub, Magdi Yacoub Heart Foundation
- Investigators
- Magdi H Yacoub, OM FRS, Study chair, Magdi Yacoub Heart Foundation - Aswan Heart Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03835676
- Sponsor's protocol ID
- Treprostinil RV
- Status last verified
- Dec 2022
- First submitted
- 6 Feb 2019
- Last updated
- 15 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Handoko ML, de Man FS, Allaart CP, Paulus WJ, Westerhof N, Vonk-Noordegraaf A. Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart. Eur Respir Rev. 2010 Mar;19(115):72-82. doi: 10.1183/09059180.00007109.
PubMed 20956170Benza R, Biederman R, Murali S, Gupta H. Role of cardiac magnetic resonance imaging in the management of patients with pulmonary arterial hypertension. J Am Coll Cardiol. 2008 Nov 18;52(21):1683-92. doi: 10.1016/j.jacc.2008.08.033.
PubMed 19007687Boxt LM, Katz J, Kolb T, Czegledy FP, Barst RJ. Direct quantitation of right and left ventricular volumes with nuclear magnetic resonance imaging in patients with primary pulmonary hypertension. J Am Coll Cardiol. 1992 Jun;19(7):1508-15. doi: 10.1016/0735-1097(92)90611-p.
PubMed 1593046Quaife RA, Chen MY, Lynch D, Badesch DB, Groves BM, Wolfel E, Robertson AD, Bristow MR, Voelkel NF. Importance of right ventricular end-systolic regional wall stress in idiopathic pulmonary arterial hypertension: a new method for estimation of right ventricular wall stress. Eur J Med Res. 2006 May 5;11(5):214-20.
PubMed 16723296McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J; American College of Cardiology Foundation Task Force on Expert Consensus Documents; American Heart Association; American College of Chest Physicians; American Thoracic Society, Inc; Pulmonary Hypertension Association. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009 Apr 28;53(17):1573-619. doi: 10.1016/j.jacc.2009.01.004. No abstract available.
PubMed 19389575Hinderliter AL, Willis PW 4th, Long W, Clarke WR, Ralph D, Caldwell EJ, Williams W, Ettinger NA, Hill NS, Summer WR, de Biosblanc B, Koch G, Li S, Clayton LM, Jobsis MM, Crow JW. Frequency and prognostic significance of pericardial effusion in primary pulmonary hypertension. PPH Study Group. Primary pulmonary hypertension. Am J Cardiol. 1999 Aug 15;84(4):481-4, A10. doi: 10.1016/s0002-9149(99)00342-2.
PubMed 10468096Barst RJ, Rubin LJ, McGoon MD, Caldwell EJ, Long WA, Levy PS. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med. 1994 Sep 15;121(6):409-15. doi: 10.7326/0003-4819-121-6-199409150-00003.
PubMed 8053614Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S, Badesch DB, Groves BM, Tapson VF, Bourge RC, Brundage BH, Koerner SK, Langleben D, Keller CA, Murali S, Uretsky BF, Clayton LM, Jobsis MM, Blackburn SD, Shortino D, Crow JW; Primary Pulmonary Hypertension Study Group. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996 Feb 1;334(5):296-301. doi: 10.1056/NEJM199602013340504.
PubMed 8532025Sebbag I, Rudski LG, Therrien J, Hirsch A, Langleben D. Effect of chronic infusion of epoprostenol on echocardiographic right ventricular myocardial performance index and its relation to clinical outcome in patients with primary pulmonary hypertension. Am J Cardiol. 2001 Nov 1;88(9):1060-3. doi: 10.1016/s0002-9149(01)01995-6. No abstract available.
PubMed 11704014Roeleveld RJ, Vonk-Noordegraaf A, Marcus JT, Bronzwaer JG, Marques KM, Postmus PE, Boonstra A. Effects of epoprostenol on right ventricular hypertrophy and dilatation in pulmonary hypertension. Chest. 2004 Feb;125(2):572-9. doi: 10.1378/chest.125.2.572.
PubMed 14769740Bristow MR, Zisman LS, Lowes BD, Abraham WT, Badesch DB, Groves BM, Voelkel NF, Lynch DM, Quaife RA. The pressure-overloaded right ventricle in pulmonary hypertension. Chest. 1998 Jul;114(1 Suppl):101S-106S. doi: 10.1378/chest.114.1_supplement.101s. No abstract available.
PubMed 9676654Vachiery JL, Hill N, Zwicke D, Barst R, Blackburn S, Naeije R. Transitioning from i.v. epoprostenol to subcutaneous treprostinil in pulmonary arterial hypertension. Chest. 2002 May;121(5):1561-5. doi: 10.1378/chest.121.5.1561.
PubMed 12006444McNulty MJ, Sailstad JM, Steffen RP. The pharmacokinetics and pharmacodynamics of the prostacyclin analog 15AU81 in the anesthetized beagle dog. Prostaglandins Leukot Essent Fatty Acids. 1993 Feb;48(2):159-66. doi: 10.1016/0952-3278(93)90105-6.
PubMed 8446654Laliberte K, Arneson C, Jeffs R, Hunt T, Wade M. Pharmacokinetics and steady-state bioequivalence of treprostinil sodium (Remodulin) administered by the intravenous and subcutaneous route to normal volunteers. J Cardiovasc Pharmacol. 2004 Aug;44(2):209-14. doi: 10.1097/00005344-200408000-00010.
PubMed 15243302Simonneau G, Barst RJ, Galie N, Naeije R, Rich S, Bourge RC, Keogh A, Oudiz R, Frost A, Blackburn SD, Crow JW, Rubin LJ; Treprostinil Study Group. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2002 Mar 15;165(6):800-4. doi: 10.1164/ajrccm.165.6.2106079.
PubMed 11897647
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Treprostinil on Right Ventricular Structure and Function in Patients With Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT03835676
- Acronym / sponsor ID
- Treprostinil RV
- Conditions
- Pulmonary Hypertension
- Keywords
- Pulmonary hypertension, Right ventricular function
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Magdi H. YacoubUniversity, hospital or other
- Study start
- 1 May 2019 (actual)
- Primary completion
- 1 Jun 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 8 Feb 2019 (actual)
- 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.
In a group of patients with PAH treated with treprostinil, the current study aims to investigate the effect of treatment on RV structure and function; and correlate changes in RV structure and function with: World Health Organisation (WHO) class, Six-minute walk test, Quality of life (QoL), and Pre-specified biomarkers (N-terminal B-type natriuretic peptide (NT-ProBNP), Tissue growth factor-B B-type natriuretic peptide BNP, and Profibrotic markers)
Detailed description
- Right ventricle (RV) in pulmonary hypertension
RV failure is the main cause of death in patients with pulmonary arterial hypertension (PAH), and the ability of the RV to adapt to the progressive increase in pulmonary vascular resistance associated with changes to the pulmonary vasculature in PAH is the main determinant of a patient's functional capacity and survival.
The response of the right ventricle (RV) to the increase in afterload produced by the pulmonary vascular changes characteristic of PAH is the key factor in the development of symptoms and in determining survival. Structurally, rising systolic and diastolic ventricular pressures increase diastolic and systolic stretch on the RV wall, which leads initially to an increase in muscle mass (adaptive hypertrophy) due to increased protein synthesis and an increase in cardiomyocyte size through the addition of sarcomeres. However, the RV cannot maintain adaptive hypertrophy in the face of sustained pressure overload, and eventually there is a transition to dilatation. At this stage there is no further increase, or even a decrease, in RV contractility, despite a further increase in load. One consequence of RV dilatation is an increase in wall tension, which increases myocardial oxygen demand and simultaneously decreases RV perfusion, leading to further compromised contractility and dilatation.
The exact mechanisms leading to the development of RV failure in patients with PAH are still unclear. Several mechanisms have been hypothesized: RV myocardial ischaemia, microvascular endothelial cell dysfunction, and myocyte apoptosis. In severe end-stage PAH, the RV changes its shape from the normal conformation to a more spherical one, and RV wall stress increases because RV wall thickness does not increase proportionally.
Given the importance of the RV in PAH, preservation and improvement of its function should be important aspects of therapy; however, there are currently few data specifically related to this aspect of treatment response.
- Vasodilator therapy and RV in pulmonary hypertension Although RV failure is the main cause of death in patients with pulmonary arterial hypertension (PAH), there is insufficient data about the effects of PAH treatment on RV geometry and function mainly because the RV assessment has been hampered by its complex crescentic shape, large infundibulum, and its trabecular nature. . This is specifically true for vasodilator therapies. Such therapies may affect the RV via direct cardiac-specific effects or indirect effects by reducing RV load. In a meta-analysis of clinical studies of PAH-specific therapies, active treatment was associated with a reduction in pulmonary vascular resistance which was accompanied by a decrease in pulmonary artery pressure, and an increase in stroke volume, but without an increase in contractility, suggesting that current PAH therapies have predominantly pulmonary vasodilating effects and have limited cardiac-specific effects. In a study of epoprostenol therapy, beneficial effects on RV structure and function (RV dilatation, curvature of the interventricular septum and maximal tricuspid regurgitant jet velocity) compared with placebo were reported following 12 weeks of treatment, with change in 6-min walk distance between baseline and 12 weeks being inversely related to the change in diastolic eccentricity index and pericardial effusion size. Such improvements may contribute to the clinical improvement and prolonged survival observed with epoprostenol in other studies.
Other evidence of improvements in RV parameters has come from descriptive studies using a number of PAH-specific therapies; however, these generally include a small number of patients, and this, together with the fact that such studies evaluated different parameters (both in terms of functional parameters and measures of RV size/mass), makes the assessment of results difficult. longer term studies of epoprostenol have not shown a positive treatment effect on RV size/mass although without a comparator arm it is not possible to determine whether long-term therapy slowed down the rate of RV hypertrophy or dilatation.
Overall, therefore, the effects of PAH-specific therapies on RV function remain to be fully investigated.
- Treprostinil Treprostinil is a tricyclic benzindene analogue of prostacyclin, and has as such similar anti-platelet and vasodilatory actions, including acute pulmonary vasodilation.
Treprostinil, a stable prostacyclin analog, has similar pharmacologic effects to epoprostenol, However, in contrast to epoprostenol, treprostinil is chemically stable at room temperature and neutral 'power of hydrogen' (pH) and has a longer half-life (elimination half-life of 4.5 h with distribution half-life of 40 min, compared with 2 to 3 min for epoprostenol) permitting continuous subcutaneous infusion (16). Treprostinil has been shown in a large multicenter randomized controlled trial to improve exercise capacity, clinical state, functional class, pulmonary hemodynamics, and quality of life in patients with pulmonary arterial hypertension.
- Assessment of RV with cardiac magnetic resonance imaging Currently, the most widely used noninvasive techniques are echocardiography and cardiac magnetic resonance imaging), and a number of potential indicators assessed using these methods have been proposed. Cardiac magnetic resonance imaging provides a higher spatial resolution, and is not limited by factors affecting echocardiography (e.g. acoustic window). Cardiac magnetic resonance imaging allows for the visualisation and measurement of complex three-dimensional geometry and it is therefore particularly suited to the complex morphology of the RV. Precise, noninvasive assessment of cardiac volumes and function is possible, without the need for geometric approximations, while assessments such as flow measurements in the heart and great vessels using techniques such as cine phase-contrast provide more comprehensive data on cardiac function than echocardiography.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- In a group of patients with PAH treated with treprostinil, the current study aims to investigate the effect of treatment on RV structure and function; and correlate changes in RV structure and function with: WHO class, Six-minute walk test, Quality of life (QoL), and Pre-specified biomarkers (NT-ProBNP, Tissue growth factor-B BNP, and Profibrotic markers)
| Arm | Type | Receives |
|---|---|---|
| Pulmonary hypertension treated with Treprostinil | Experimental | Drug: TreprostinilThirty patients who will be treated with Treprostinil. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
Key exclusion criteria (7 listed)
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 |
|---|---|---|
| TreprostinilAlso: RemodulinAfter inclusion and baseline measurements, patients will receive treprostinil in addition to background therapy for 24 months. Follow-up assessment will include: * Clinical, echocardiographic, laboratory assessments will be repeated at 1, 3, 6, 12, 18, and 24 month (or when there is clinical indication) * CMR will be performed at 6 monthly intervals for 2 years. * Peak power output at 6,12, 18 and 24 month * Right-side cardiac catheterization will be performed at 6, 12 , 18 and 24 months (or when there is clinical indication) | Drug | Pulmonary hypertension treated with Treprostinil |
Primary outcome
Assessment of Treprostinil effects on right ventricular structure and function using echocardiography
Time frame: through study completion, an average of 5 years
Assessment of RV structure and function by echocardiography
Assessment of Treprostinil effects on right ventricular structure and function using Cardiac Magnetic Resonance Imaging (CMR).
Time frame: through study completion, an average of 5 years
Assessment of RV structure and function by cardiac magnetic resonance imaging (CMR).
4 secondary outcomes
Correlate changes in RV structure and function with World Health Organisation (WHO) Class.
Time frame: through study completion, an average of 5 years
Correlate changes in RV structure and function with the Six-minute walk test results
Time frame: through study completion, an average of 5 years
Correlate changes in RV structure and function with QoL
Time frame: through study completion, an average of 5 years
Correlate changes in RV structure and function with prespecified biomarkers
Time frame: through study completion, an average of 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2022.
- Background: PubMed 20956170Handoko ML, de Man FS, Allaart CP, Paulus WJ, Westerhof N, Vonk-Noordegraaf A. Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart. Eur Respir Rev. 2010 Mar;19(115):72-82. doi: 10.1183/09059180.00007109.
- Background: PubMed 19007687Benza R, Biederman R, Murali S, Gupta H. Role of cardiac magnetic resonance imaging in the management of patients with pulmonary arterial hypertension. J Am Coll Cardiol. 2008 Nov 18;52(21):1683-92. doi: 10.1016/j.jacc.2008.08.033.
- Background: PubMed 1593046Boxt LM, Katz J, Kolb T, Czegledy FP, Barst RJ. Direct quantitation of right and left ventricular volumes with nuclear magnetic resonance imaging in patients with primary pulmonary hypertension. J Am Coll Cardiol. 1992 Jun;19(7):1508-15. doi: 10.1016/0735-1097(92)90611-p.
- Background: PubMed 16723296Quaife RA, Chen MY, Lynch D, Badesch DB, Groves BM, Wolfel E, Robertson AD, Bristow MR, Voelkel NF. Importance of right ventricular end-systolic regional wall stress in idiopathic pulmonary arterial hypertension: a new method for estimation of right ventricular wall stress. Eur J Med Res. 2006 May 5;11(5):214-20.
- Background: PubMed 19389575McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J; American College of Cardiology Foundation Task Force on Expert Consensus Documents; American Heart Association; American College of Chest Physicians; American Thoracic Society, Inc; Pulmonary Hypertension Association. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009 Apr 28;53(17):1573-619. doi: 10.1016/j.jacc.2009.01.004. No abstract available.
- Background: PubMed 10468096Hinderliter AL, Willis PW 4th, Long W, Clarke WR, Ralph D, Caldwell EJ, Williams W, Ettinger NA, Hill NS, Summer WR, de Biosblanc B, Koch G, Li S, Clayton LM, Jobsis MM, Crow JW. Frequency and prognostic significance of pericardial effusion in primary pulmonary hypertension. PPH Study Group. Primary pulmonary hypertension. Am J Cardiol. 1999 Aug 15;84(4):481-4, A10. doi: 10.1016/s0002-9149(99)00342-2.
- Background: PubMed 8053614Barst RJ, Rubin LJ, McGoon MD, Caldwell EJ, Long WA, Levy PS. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med. 1994 Sep 15;121(6):409-15. doi: 10.7326/0003-4819-121-6-199409150-00003.
- Background: PubMed 8532025Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S, Badesch DB, Groves BM, Tapson VF, Bourge RC, Brundage BH, Koerner SK, Langleben D, Keller CA, Murali S, Uretsky BF, Clayton LM, Jobsis MM, Blackburn SD, Shortino D, Crow JW; Primary Pulmonary Hypertension Study Group. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996 Feb 1;334(5):296-301. doi: 10.1056/NEJM199602013340504.
- Background: PubMed 11704014Sebbag I, Rudski LG, Therrien J, Hirsch A, Langleben D. Effect of chronic infusion of epoprostenol on echocardiographic right ventricular myocardial performance index and its relation to clinical outcome in patients with primary pulmonary hypertension. Am J Cardiol. 2001 Nov 1;88(9):1060-3. doi: 10.1016/s0002-9149(01)01995-6. No abstract available.
- Background: PubMed 14769740Roeleveld RJ, Vonk-Noordegraaf A, Marcus JT, Bronzwaer JG, Marques KM, Postmus PE, Boonstra A. Effects of epoprostenol on right ventricular hypertrophy and dilatation in pulmonary hypertension. Chest. 2004 Feb;125(2):572-9. doi: 10.1378/chest.125.2.572.
- Background: PubMed 9676654Bristow MR, Zisman LS, Lowes BD, Abraham WT, Badesch DB, Groves BM, Voelkel NF, Lynch DM, Quaife RA. The pressure-overloaded right ventricle in pulmonary hypertension. Chest. 1998 Jul;114(1 Suppl):101S-106S. doi: 10.1378/chest.114.1_supplement.101s. No abstract available.
- Background: PubMed 12006444Vachiery JL, Hill N, Zwicke D, Barst R, Blackburn S, Naeije R. Transitioning from i.v. epoprostenol to subcutaneous treprostinil in pulmonary arterial hypertension. Chest. 2002 May;121(5):1561-5. doi: 10.1378/chest.121.5.1561.
- Individual participant dataSharing planned: No
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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.
Magdi H Yacoub, OM FRS study chair
Magdi Yacoub Heart Foundation - Aswan Heart Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Treprostinil in people with Pulmonary Hypertension, run by Magdi H. Yacoub at 1 site in Egypt.
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 5 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 15 Dec 2022. 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 Egypt. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ahmed M ElGuindy, MD, MRCP (+201001615151, ahmed_elguindy@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of Treprostinil effects on right ventricular structure and function using echocardiography (time frame: through study completion, an average of 5 years). The study lists 2 primary outcomes in all. 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 NCT03835676, which also lists 20 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 15 Dec 2022.