Effects of Treprostinil on Right Ventricular Structure and Function in Patients With Pulmonary Arterial Hypertension

NCT03835676 | Unknown Phase 4 DMC

• 1 other identifier: Treprostinil RV
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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 biomarkers (N-terminal B-type natriuretic peptide (NT-ProBNP), Tissue growth factor-B B-type natriuretic peptide BNP, and Profibrotic markers)

Conditions

Pulmonary Hypertension

Keywords

Pulmonary hypertension; Right ventricular function

Outcome Measures

Primary Outcomes (2)

• Assessment of Treprostinil effects on right ventricular structure and function using echocardiography

  Assessment of RV structure and function by echocardiography

  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).

  through study completion, an average of 5 years

Secondary Outcomes (4)

• Correlate changes in RV structure and function with World Health Organisation (WHO) Class.

  through study completion, an average of 5 years

• Correlate changes in RV structure and function with the Six-minute walk test results

  through study completion, an average of 5 years

• Correlate changes in RV structure and function with QoL

  through study completion, an average of 5 years

• Correlate changes in RV structure and function with prespecified biomarkers

  through study completion, an average of 5 years

Study Arms (1)

Pulmonary hypertension treated with Treprostinil

EXPERIMENTAL

Thirty patients who will be treated with Treprostinil.

Drug: Treprostinil

Interventions

Treprostinil DRUG

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)

Also known as: Remodulin

Pulmonary hypertension treated with Treprostinil

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Magdi H. Yacoub: lead

Study Sites (1)

Aswan Heart Centre - Magdi Yacoub Heart Foundation

Aswān, Egypt

RECRUITING

Related Publications (20)

• 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.

  PMID: 20956170 BACKGROUND

• Benza 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.

  PMID: 19007687 BACKGROUND

• Boxt 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.

  PMID: 1593046 BACKGROUND

• Quaife 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.

  PMID: 16723296 BACKGROUND

• McLaughlin 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.

  PMID: 19389575 BACKGROUND

• Hinderliter 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.

  PMID: 10468096 BACKGROUND

• Barst 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.

  PMID: 8053614 BACKGROUND

• Barst 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.

  PMID: 8532025 BACKGROUND

• Sebbag 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.

  PMID: 11704014 BACKGROUND

• Roeleveld 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.

  PMID: 14769740 BACKGROUND

• Bristow 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.

  PMID: 9676654 BACKGROUND

• Vachiery 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.

  PMID: 12006444 BACKGROUND

• McNulty 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.

  PMID: 8446654 BACKGROUND

• Laliberte 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.

  PMID: 15243302 BACKGROUND

• Simonneau 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.

  PMID: 11897647 BACKGROUND

• Gomberg-Maitland M, Tapson VF, Benza RL, McLaughlin VV, Krichman A, Widlitz AC, Barst RJ. Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension. Am J Respir Crit Care Med. 2005 Dec 15;172(12):1586-9. doi: 10.1164/rccm.200505-766OC. Epub 2005 Sep 8.

  PMID: 16151039 BACKGROUND

• Kovacs G, Reiter G, Reiter U, Rienmuller R, Peacock A, Olschewski H. The emerging role of magnetic resonance imaging in the diagnosis and management of pulmonary hypertension. Respiration. 2008;76(4):458-70. doi: 10.1159/000158548. Epub 2008 Nov 12.

  PMID: 19018164 BACKGROUND

• Towbin JA. Scarring in the heart--a reversible phenomenon? N Engl J Med. 2007 Oct 25;357(17):1767-8. doi: 10.1056/NEJMcibr075397. No abstract available.

  PMID: 17960018 BACKGROUND

• Zannad F, Alla F, Dousset B, Perez A, Pitt B. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation. 2000 Nov 28;102(22):2700-6. doi: 10.1161/01.cir.102.22.2700.

  PMID: 11094035 BACKGROUND

• Morais P, Marchi A, Bogaert JA, Dresselaers T, Heyde B, D'hooge J, Bogaert J. Cardiovascular magnetic resonance myocardial feature tracking using a non-rigid, elastic image registration algorithm: assessment of variability in a real-life clinical setting. J Cardiovasc Magn Reson. 2017 Feb 17;19(1):24. doi: 10.1186/s12968-017-0333-y.

  PMID: 28209163 BACKGROUND

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

treprostinil

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Magdi H Yacoub, OM FRS

  Magdi Yacoub Heart Foundation - Aswan Heart Centre

  STUDY CHAIR

Central Study Contacts

Ahmed M ElGuindy, MD, MRCP

CONTACT

+201001615151; ahmed_elguindy@hotmail.com

Shehab M Anwer, MBBCh., MRes

CONTACT

+41788816333; shehabanwer@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator - Sir. Prof., OM FRS

Model Details: 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)

Study Record Dates

• First Submitted: February 6, 2019
• First Posted: February 8, 2019
• Study Start: May 1, 2019
• Primary Completion: June 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 15, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)