Clinical trial NCT00370214: REVEAL Registry™: Registry to Evaluate Early And Long-term PAH Disease Management
Official title: REVEAL Registry™: Registry to Evaluate Early And Long-term PAH Disease Management
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pulmonary Hypertension
Keywords: Pulmonary arterial hypertension
Lung diseases
Heart diseases
Pulmonary circulation
Vascular resistance
PAH
Hypertension
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2006-08-31
Enrollment: 3515
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with WHO Group I Pulmonary Arterial Hypertension from US based PAH centers.

Brief summary: The REVEAL Registry™ is a multicenter, observational, U.S.-based study of the clinical course and disease management of pulmonary arterial hypertension (PAH) patients. All consecutive consenting patients diagnosed with WHO Group I PAH according to specific hemodynamic criteria at participating institutions will be enrolled. Participating patients will be followed for a minimum of five years from the time of enrollment.

Detailed description: Pulmonary arterial hypertension (PAH) is a chronic, progressive, and often fatal disease characterized by severe constriction of the blood vessels in the lungs. Over the past decade, significant strides have been made in the medical management and understanding of PAH. However, much remains to be learned about the clinical course of both idiopathic PAH and associated PAH, including clinical presentation, pace of progression, key parameters to monitor, impact of treatment, and prognosticators of outcome. As the unique body of knowledge generated by the REVEAL Registry grows, it is hoped that new understandings, insights, and treatments will emerge that will improve the lives of patients with PAH.

The REVEAL Registry will provide investigators with descriptive data regarding the clinical course and treatment outcomes in patients with WHO Group I PAH. Data derived from the study may offer important tools for assessing current management practices of treating investigators, as well as changes over time. Additionally, the relationship of patient- and disease-specific parameters to patient outcomes may be able to be assessed through analysis of data from this study.

The specific objectives of the REVEAL Registry™ are to:

* Characterize the demographics and clinical course of PAH patients
* Evaluate and compare patient outcomes
* Identify clinical predictors of short-term and long-term clinical outcomes
* Assess the relationship between PAH medications and patient outcomes
* Report temporal trends in treatments and outcomes for newly diagnosed patients
* Collect timely and relevant data for the evolving research needs of the PAH community

Eligibility criteria: Inclusion Criteria:

* Newly diagnosed or previously diagnosed patients with WHO Group I PAH.
* Documentation of the following hemodynamic parameters by right heart catheterization, performed at any time prior to study enrollment:
* Mean pulmonary arterial pressure (mPAP) \>25 mm Hg at rest or mPAP \> 30 mm Hg with exercise contemporaneous with a pulmonary wedge pressure ≤ 18 mm Hg
* Pulmonary wedge pressure ≤ 18 mm Hg
* Pulmonary vascular resistance (PVR) ≥ 240 dynes.sec.cm-5 (i.e., ≥ 3.0 Wood units)

Exclusion Criteria:

* Patients who meet the criteria for inclusion into WHO Groups II, III, IV or V
* Have not had documentation of hemodynamic criteria for PAH by right heart catheterization at some time preceding study entry and following development of symptoms associated with PAH.
* Do not meet the required hemodynamic criteria for entry into the study

Primary outcomes:
measure: Survival
timeFrame: 5 years
Secondary outcomes:
measure: clinical predictors, precise outcome definitions
timeFrame: 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: University of Arizona Medical Center
state: Arizona
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Los Angeles
country: United States
facility: UCLA / VA Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: San Francisco
country: United States
facility: Univeristy of California, San Francisco - Division of Cardiology and Pediatric ICU
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Torrance
country: United States
facility: UCLA School of Medicine: Harbor-UCLA
state: California
city: Denver
country: United States
facility: The Children's Hospital
state: Colorado
city: Denver
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Sarasota
country: United States
facility: Suncoast Lung Center
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Hospitals
state: Illinois
city: Naperville
country: United States
facility: Midwest Heart Foundation
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Health Care
state: Iowa
city: Louisville
country: United States
facility: Kentucky Pulmonary Associates
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Tufts-New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospitals
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Cleveland
country: United States
facility: University Hospital of Cleveland
state: Ohio
city: Columbus
country: United States
facility: Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: Legacy Pulmonary Hypertension Clinic
state: Oregon
city: Philadelphia
country: United States
facility: Penn Presbyterian Medial Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple Lung Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: University Texas Health Science Center
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Falls Church
country: United States
facility: Inova Heart and Vascular Institute
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's
state: Washington
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: Mayo Clinic - Rochester, Minnesota
name: Michael D. McGoon, M.D.
role: STUDY_CHAIR
affiliation: University of Colorado, Denver
name: David B. Badesch, M.D.
role: STUDY_DIRECTOR
affiliation: Columbia University
name: Robyn J. Barst, M.D.
role: STUDY_DIRECTOR
affiliation: University of Alabama at Birmingham
name: Raymond Benza, M.D.
role: STUDY_DIRECTOR
affiliation: LDS Hospital
name: Gregory Elliott, M.D.
role: STUDY_DIRECTOR
affiliation: Boston Medical Center
name: Harrison Farber, M.D.
role: STUDY_DIRECTOR
affiliation: Baylor College of Medicine
name: Adaani Frost, M.D.
role: STUDY_DIRECTOR
affiliation: Duke University Pulmonary Vascular Disease Center
name: Abby Krichman, RRT
role: STUDY_DIRECTOR
References:
citation: Benza RL, Kanwar MK, Raina A, Scott JV, Zhao CL, Selej M, Elliott CG, Farber HW. Development and Validation of an Abridged Version of the REVEAL 2.0 Risk Score Calculator, REVEAL Lite 2, for Use in Patients With Pulmonary Arterial Hypertension. Chest. 2021 Jan;159(1):337-346. doi: 10.1016/j.chest.2020.08.2069. Epub 2020 Sep 1.
citation: Torbicki A, Bacchi M, Delcroix M, Farber HW, Ghofrani HA, Hennessy B, Jansa P, Mehta S, Perchenet L, Pulido T, Rosenberg D, Rubin LJ, Sastry BKS, Simonneau G, Sitbon O, Souza R, Wei LJ, Channick R, Benza R. Integrating Data From Randomized Controlled Trials and Observational Studies to Assess Survival in Rare Diseases. Circ Cardiovasc Qual Outcomes. 2019 May;12(5):e005095. doi: 10.1161/CIRCOUTCOMES.118.005095.
citation: Benza RL, Gomberg-Maitland M, Elliott CG, Farber HW, Foreman AJ, Frost AE, McGoon MD, Pasta DJ, Selej M, Burger CD, Frantz RP. Predicting Survival in Patients With Pulmonary Arterial Hypertension: The REVEAL Risk Score Calculator 2.0 and Comparison With ESC/ERS-Based Risk Assessment Strategies. Chest. 2019 Aug;156(2):323-337. doi: 10.1016/j.chest.2019.02.004. Epub 2019 Feb 14.
citation: Preston IR, Roberts KE, Miller DP, Sen GP, Selej M, Benton WW, Hill NS, Farber HW. Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL). Circulation. 2015 Dec 22;132(25):2403-11. doi: 10.1161/CIRCULATIONAHA.115.018435. Epub 2015 Oct 28.
citation: Farber HW, Miller DP, Poms AD, Badesch DB, Frost AE, Muros-Le Rouzic E, Romero AJ, Benton WW, Elliott CG, McGoon MD, Benza RL. Five-Year outcomes of patients enrolled in the REVEAL Registry. Chest. 2015 Oct;148(4):1043-54. doi: 10.1378/chest.15-0300.
citation: Chung L, Farber HW, Benza R, Miller DP, Parsons L, Hassoun PM, McGoon M, Nicolls MR, Zamanian RT. Unique predictors of mortality in patients with pulmonary arterial hypertension associated with systemic sclerosis in the REVEAL registry. Chest. 2014 Dec;146(6):1494-1504. doi: 10.1378/chest.13-3014.
citation: Burger CD, Long PK, Shah MR, McGoon MD, Miller DP, Romero AJ, Benton WW, Safford RE. Characterization of first-time hospitalizations in patients with newly diagnosed pulmonary arterial hypertension in the REVEAL registry. Chest. 2014 Nov;146(5):1263-1273. doi: 10.1378/chest.14-0193.
citation: Frost AE, Badesch DB, Miller DP, Benza RL, Meltzer LA, McGoon MD. Evaluation of the predictive value of a clinical worsening definition using 2-year outcomes in patients with pulmonary arterial hypertension: a REVEAL Registry analysis. Chest. 2013 Nov;144(5):1521-1529. doi: 10.1378/chest.12-3023.
citation: Bersohn MM, Turner MP, Traiger GL, Frost AE, Shapiro S. Systemic BP and heart rate as prognostic indicators in pulmonary arterial hypertension. Chest. 2013 Sep;144(3):959-965. doi: 10.1378/chest.12-2572.
citation: Barst RJ, Chung L, Zamanian RT, Turner M, McGoon MD. Functional class improvement and 3-year survival outcomes in patients with pulmonary arterial hypertension in the REVEAL Registry. Chest. 2013 Jul;144(1):160-168. doi: 10.1378/chest.12-2417.
citation: Poms AD, Turner M, Farber HW, Meltzer LA, McGoon MD. Comorbid conditions and outcomes in patients with pulmonary arterial hypertension: a REVEAL registry analysis. Chest. 2013 Jul;144(1):169-176. doi: 10.1378/chest.11-3241.
citation: Kitterman N, Poms A, Miller DP, Lombardi S, Farber HW, Barst RJ. Bloodstream infections in patients with pulmonary arterial hypertension treated with intravenous prostanoids: insights from the REVEAL REGISTRY(R). Mayo Clin Proc. 2012 Sep;87(9):825-34. doi: 10.1016/j.mayocp.2012.05.014. Epub 2012 Aug 9.
citation: Frost AE, Farber HW, Barst RJ, Miller DP, Elliott CG, McGoon MD. Demographics and outcomes of patients diagnosed with pulmonary hypertension with pulmonary capillary wedge pressures 16 to 18 mm Hg: insights from the REVEAL Registry. Chest. 2013 Jan;143(1):185-195. doi: 10.1378/chest.11-1387.
citation: Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 2012 Aug;142(2):448-456. doi: 10.1378/chest.11-1460.
citation: Barst RJ, McGoon MD, Elliott CG, Foreman AJ, Miller DP, Ivy DD. Survival in childhood pulmonary arterial hypertension: insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management. Circulation. 2012 Jan 3;125(1):113-22. doi: 10.1161/CIRCULATIONAHA.111.026591. Epub 2011 Nov 15.
citation: Krowka MJ, Miller DP, Barst RJ, Taichman D, Dweik RA, Badesch DB, McGoon MD. Portopulmonary hypertension: a report from the US-based REVEAL Registry. Chest. 2012 Apr;141(4):906-915. doi: 10.1378/chest.11-0160. Epub 2011 Jul 21.
citation: Shapiro S, Traiger GL, Turner M, McGoon MD, Wason P, Barst RJ. Sex differences in the diagnosis, treatment, and outcome of patients with pulmonary arterial hypertension enrolled in the registry to evaluate early and long-term pulmonary arterial hypertension disease management. Chest. 2012 Feb;141(2):363-373. doi: 10.1378/chest.10-3114. Epub 2011 Jul 14.
citation: Benza RL, Gomberg-Maitland M, Miller DP, Frost A, Frantz RP, Foreman AJ, Badesch DB, McGoon MD. The REVEAL Registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension. Chest. 2012 Feb;141(2):354-362. doi: 10.1378/chest.11-0676. Epub 2011 Jun 16.
citation: Brown LM, Chen H, Halpern S, Taichman D, McGoon MD, Farber HW, Frost AE, Liou TG, Turner M, Feldkircher K, Miller DP, Elliott CG. Delay in recognition of pulmonary arterial hypertension: factors identified from the REVEAL Registry. Chest. 2011 Jul;140(1):19-26. doi: 10.1378/chest.10-1166. Epub 2011 Mar 10.
citation: Burger CD, Foreman AJ, Miller DP, Safford RE, McGoon MD, Badesch DB. Comparison of body habitus in patients with pulmonary arterial hypertension enrolled in the Registry to Evaluate Early and Long-term PAH Disease Management with normative values from the National Health and Nutrition Examination Survey. Mayo Clin Proc. 2011 Feb;86(2):105-12. doi: 10.4065/mcp.2010.0394.
citation: Benza RL, Miller DP, Gomberg-Maitland M, Frantz RP, Foreman AJ, Coffey CS, Frost A, Barst RJ, Badesch DB, Elliott CG, Liou TG, McGoon MD. Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation. 2010 Jul 13;122(2):164-72. doi: 10.1161/CIRCULATIONAHA.109.898122. Epub 2010 Jun 28.
citation: Frost AE, Badesch DB, Barst RJ, Benza RL, Elliott CG, Farber HW, Krichman A, Liou TG, Raskob GE, Wason P, Feldkircher K, Turner M, McGoon MD. The changing picture of patients with pulmonary arterial hypertension in the United States: how REVEAL differs from historic and non-US Contemporary Registries. Chest. 2011 Jan;139(1):128-37. doi: 10.1378/chest.10-0075. Epub 2010 Jun 17.
citation: Chung L, Liu J, Parsons L, Hassoun PM, McGoon M, Badesch DB, Miller DP, Nicolls MR, Zamanian RT. Characterization of connective tissue disease-associated pulmonary arterial hypertension from REVEAL: identifying systemic sclerosis as a unique phenotype. Chest. 2010 Dec;138(6):1383-94. doi: 10.1378/chest.10-0260. Epub 2010 May 27.