Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension (TOPP-2)

The TOPP-2 registry is an international, non-interventional, prospective registry including children and adolescents newly diagnosed with pulmonary hypertension (PH) to gain further insights in the disease course and long-term outcome of PH in childhood.

Patients will undergo clinical assessments and receive standard medical care, as determined by treating physicians in their daily clinical practice. The TOPP-2 registry is specifically designed to capture the variables that have been proposed as treatment goals in PePH and the reasons for changes in treatment strategy.

The TOPP-2 registry uses the new clinical classification of PH as outlined at the 5th World Symposium for Pulmonary Hypertension (WSPH) in Nice 2013 and includes new characterizations for children with PH.

The registry is planned and implemented under the scientific leadership of the Association for Pediatric Pulmonary Hypertension (PePH), independently from the financial sponsors.

All enrolled patients will have a follow-up period of 18 months.

Study Overview

• Status: Completed
• Conditions: Hypertension, Pulmonary

• Study Type: Observational
• Enrollment (Actual): 388

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia, 3052
    • Royal Children's Hospital
• Brazil
  • São Paulo, Brazil, 05403-000
    • University of Sao Paulo
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1XB
      • The Hospital for Sick Children
• China
  • Beijing, China, 100037
    • Fu Wai Hospital
• Colombia
  • Bogota, Colombia
    • Hospital Pediátrico La Misericordia
• France
  • Paris, France, 75015
    • Université Paris Descartes
• Germany
  • Ulm, Germany, 89075
    • University Children's Hospital Ulm
• Hungary
  • Budapest, Hungary
    • Institute of Cardiology
• Israel
  • Jerusalem, Israel, 91120
    • Hadassah, Hebrew University Medical Center
• Italy
  • Padova, Italy, 35127
    • University of Padova
• Japan
  • Tokyo, Japan, 1438541
    • Toho Universit Omori Medical Center
  • Tokyo, Japan, 160-8582
    • Keio University
• Mexico
  • Mexico City, Mexico, 14050
    • National Heart Institute
• Netherlands
  • Groningen, Netherlands, 9700
    • Beatrix Children's Hospital, University Medical Center Groningen
• Poland
  • Warsaw, Poland, 04-730
    • Children's Memorial
• Saudi Arabia
  • Jeddah, Saudi Arabia, 23311
    • King Fahd Armed Forces Hospital
• Sweden
  • Gothenburg, Sweden, 41685
    • The Queen Silvia's Children's Hospital
• Switzerland
  • Geneva, Switzerland, 1211
    • Hôpital Des Enfants
  • Zurich, Switzerland, 8032
    • University Children's Hospital
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver School of Medicine, Children's Hospital Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St Louis Children's Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232-9310
      • Vanderbilt University Children's Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

1. Children and adolescents, newly diagnosed with PH (incident PePH patients), meeting the inclusion criteria. A patient is considered an incident patient if the time elapsed between the diagnostic RHC and the initial visit at the site including the patient is less than or equal to three months and if the time between diagnostic RHC and informed consent is less than or equal to six months
2. Ex-incident patients from the previous TOPP-1 registry.

Description

Inclusion Criteria:

• Patient must be an incident patient, i.e.newly diagnosed with PH
• Age at time of diagnosis is at least 3 months and less than 18 years

• Patients must present with PH belonging to one of the following categories

  • Group 1 according to updated Nice clinical classification
  • Group 3 according to updated Nice clinical classification
  • Group 4 according to updated Nice clinical classification
  • Group 5 according to updated Nice clinical classification
• PH confirmed by heart catheterisation (HC)
• At HC, the patient must present with mean pulmonary arterial pressure (PAP) of at least 25 mmHg at rest, a pulmonary vascular resistance index (PVRi) equal to or below 3 Wood units*m^2 and mean pulmonary arterial wedge pressure (PAWP) below or equal to 15 mmHg
• In case of congenital heart disease (CHD) patients who had undergone palliative procedure or repair to close systemic to pulmonary shunt, the diagnosis of PH must have been confirmed by HC at least 6 months after surgery/palliative procedure took place
• For patients with PAH-CHD open shunt, only those considered not operable due to advanced pulmonary vascular disease are eligible
• Patients to be included into the registry, and/or their legal guardians, must give informed consent. Where applicable patients will be asked for their written assent
• Participating sites must agree to adhere to the recommendations of the WSPH 2015 Nice, Pediatric Taskforce.

Exclusion Criteria:

• Patients belonging to Group 2 according to updated Nice clinical classification

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Death	Over registry run-time (5.5 years)
Transplantation	Over registry run-time (5.5 years)
Adverse events	Over registry run-time (5.5 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalisation related to pulmonary arterial hypertension (PAH)		Over registry run-time (5.5 years)
Use/initiation of i.v./s.c. prostanoids		Over registry run-time (5.5 years)
Atrial septostomy		Over registry run-time (5.5 years)
Potts shunt		Over registry run-time (5.5 years)
Time to clinical worsening	Various composites of above parameters	Over registry run-time (5.5 years)
Decline in 6-minute walk test (6MWT)		Over registry run-time (5.5 years)
Type of treatment	Type of treatment (drug, mono/combination, administration route)	Over registry run-time (5.5 years)
Switch in treatment		Over registry run-time (5.5 years)
Escalation of treatment		Over registry run-time (5.5 years)
Reasons for treatment change		Over registry run-time (5.5 years)
Decline in WHO functional class		Over registry run-time (5.5 years)
Decline in Panama functional class		Over registry run-time (5.5 years)
Worsening of echocardiographic parameters (ECHO)	Parameters encompass TAPSE and RV/LV dimension ratio	Over registry run-time (5.5 years)
Increase in Brain Natriuretic Peptide (BNP)		Over registry run-time (5.5 years)
Increase in N-terminal-proBNP (NT-proBNP)		Over registry run-time (5.5 years)

Collaborators and Investigators

• Sponsor: Association for Pediatric Pulmonary Hypertension
• Investigators: Study Chair: Dunbar Ivy, Prof, Association for Pediatric Pulmonary Hypertension

Publications and helpful links

Helpful Links

• Webpage of the Association for Pediatric Pulmonary Hypertension

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: November 10, 2015
• First Submitted That Met QC Criteria: November 19, 2015
• First Posted (Estimate): November 20, 2015

Study Record Updates

• Last Update Posted (Actual): April 13, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: TOPP-2