TOPP-2

Design and rationale of the TOPP-2 Registry

TOPP-2 is an international, clinician-driven, multi-center prospective observational registry collecting data on children and adolescents consecutively diagnosed with PH. Patients undergo clinical assessments and receive standard medical care, as determined by the patient's physician in centers that have declared to be committed to follow the pediatric diagnostic and follow-up guidelines, as proposed at the WSPH 2013, in their daily clinical practice. Patients do not receive (experimental) intervention or treatment as a consequence of their participation in the registry.

As this is a real-world, observational, non-interventional study design, the frequency of visits is determined by the physician and by the health care needs of the patient. Nevertheless, participating sites have declared to adhere to the guidelines, proposed by the Pediatric Taskforce at the WSPH, Nice, emphasizing the importance of continuous repeat evaluation of progression of disease in children with PH. Consistent with standard care, physicians are encouraged to schedule patient visits at least once a year. All visits will be documented in the registry.

Kindly refer to the TOPP-2 observational plan and the Clinicaltrials.gov entry for further details.

  • Patient population and inclusion criteria
  • Objectives
  • Participating sites
  • Data collection and confidentiality
  • Financial support

Patient population and inclusion criteria

The patient population documented in TOPP-2 will include:

  • Ex-incident TOPP-1 patients, meeting all inclusion criteria and who agree to continue their registry participation by signing the TOPP-2 informed consent form upon inclusion of sites who participated in TOPP-1.
  • Children and adolescents, newly diagnosed with PH (incident pediatric PH patients), meeting the inclusion criteria as listed below. A patient is considered an incident patient if the time elapsed between the diagnostic right heart catheterization and the initial visit at the site including the patient is less than or equal to three months.

Inclusion criteria:

  • PH diagnosis confirmed by heart catheterization (HC): PAP mean ≥ 25 mmHg at rest, PVRi ≥ 3 Wood Units•m2 and mPAWP ≤ 15 mmHg. Diagnosis of CHD patients who had undergone palliative procedure or repair to close systemic to pulmonary shunt must have been confirmed by HC at least 6 months after surgery/palliative procedure.
  • Aged ≥ 3 months and < 18 years old at time of diagnosis.
  • Incident PH patient (see above) who provided written consent to participate.
  • Patients must present with PH belonging to either Group 1, 3, 4 or 5 according to updated Nice clinical classification.

Patients will undergo clinical assessments and receive standard medical care, as determined by treating physicians in their daily clinical practice. The TOPP-2 follow-up case report form (CRF) is specifically designed to capture the variables that have been proposed as treatment goals in pediatric PH and the reasons for changes in treatment strategy, including clinical status, BNP/NT-proBNP levels, ECHO-cardiac assessment and initiation/change of PH-targeted therapies.

Objectives

The TOPP-2 registry aims to:

  • Validate the observed changes in the variables proposed in Nice as treatment goals in pediatric PH and identify new treatment goals.
  • Describe the frequency of components of clinical worsening in pediatric PH.
  • Evaluate the predictive value of these components and their composite of clinical worsening in pediatric PH.
  • Identify the current drivers of treatment strategy.
  • Compare the effectiveness of treatment strategies.
  • Describe disease characteristics, diagnosis, treatment and outcome in updated Nice clinical classification of pediatric PH group 3, 4 and 5 patients.
  • Characterize PAH-CHD with regard to presentation, clinical course and treatment strategy, according to the proposed ABCD system.

The TOPP-2 registry has been launched in July 2015 and the inclusion period will run for up to 3 years, allowing the inclusion of approximately 200 patients. All patients included will have a minimum follow-up of 3 years.

Participating sites

Participation in the TOPP-2 registry is upon invitation by the PePH Association based on the decision of the executive board of the Association.

Data collection and confidentiality

A web-based electronic data capture (EDC) system is used for data entry over a secured connection. Data will be encrypted when transferred over the internet and will be stored in a secure database protected from unauthorized access. Access to the patient database will be password-secured and restricted to authorized users.

In order to guarantee the anonymity of the patient data within TOPP-2, no names, initials or date of birth are stored within the system. When setting up a patient the site enters initials, date of birth and gender for the system to generate a unique patient identifier. Immediately thereafter, initials and date of birth are deleted from the database and can no longer be retrieved. A document describing the process is available on request.

An audit trail is maintained by the EDC system for all data entries and changes. This trail will indicate what the entries/changes have been, who has made them and when.

The site including patients into the registry is responsible for data entry related to this patient. Should for any reason another site try to include the same patient, the system will recognize this and inform the second site that this patient has already been included and by which site. Patients can be transferred between sites only if both sites agree to it in writing and the transfer can only be performed by the company hosting the data or the Clinical Research Organization (CRO).

The individual sites own the data entered from their patients and will be able to generate analysis reports based on data from their own site. Consolidated data from all participating sites are the property of the Association for PePH and will be analyzed on a regular basis.

Financial support

The registry is made possible through a research grant from Actelion Pharmaceuticals Ltd.

Access to the registry

Participating sites can access the registry here and the training system here.