1. AARCC Proposal October 2014
ASD-PAH
AARCC Proposal
October 2014
Coordinating/Primary Site: The Ohio State University/Nationwide Children’s Hospital
Primary Investigator: Elisa Bradley MD

2. Clinical Question:
How do we know which (ASD-PAH) patients will respond to PAH-specific medications?

3. Aim 1: In adult patients with an unrepaired ASD and severe PAH, we will quantify the mean change in functional capacity in response PAH-specific medical therapy.
Primary endpoints: Report the mean change in NYHA FC, 6MWT distance, and resting O2 in adult ASD-PAH patients that are placed on PAH-specific therapy.
Aim 2: In adults with unrepaired ASD-PAH, we will determine if there are clinical predictors that are associated with a more favorable response (patients who, after treatment with medical PAH therapy meet acceptable criteria for ASD closure: pulmonary vascular resistance (PVR) < 6 Wood units, PVR to systemic vascular resistance (SVR) ratio < 0.3, Net left-to-right shunt with pulmonary flow to systemic flow (Qp:Qs) ratio > 1.5).
Primary endpoints: Report the difference in BMI, PA diameter, TR severity, age, and invasive hemodynamics between responders and non-responders to PAH-specific medical therapy.

4. Inclusion Criteria Age > 18 years old
Documented unrepaired ASD with PAH
Invasively proven PAH at baseline (pre closure):
Mean PA (mPA) > 25mmHg
Pulmonary vascular resistance (PVR) > 3 Wood units
Pulmonary capillary wedge pressure (PCWP) < 18mmHg
Absence of complex congenital heart disease, defined per ACC Guidelines 2008 (6) See Table 2 (proposal).
No other etiologies for PAH
Patient must have pre-PAH therapy hemodynamic catheterization and a second hemodynamic catheterization after ≥ 6 months of medical therapy.
Patients must have a 6-MWT pre-PAH therapy and after ≥ 6 months of medical therapy for PAH
If the ASD was closed, hemodynamic catheterization prior to (or at the time of) closure must be available.

5. Section A: General Information Section B: Demographics/Baseline Data
Components of the Case Report Form (CRF)
Section A: General Information
Section B: Demographics/Baseline Data
Section C: Treatment and Closure Data
Section D: 6 Minute Walk Test, functional class, BNP
Section E: Echocardiographic Data
Section F: Hemodynamic Data (right heart catheterization)

6. Sections D,E,F,G – Table Format 6 Minute Walk Test
Date (MM/YY)
Distance walked (feet)
Oxygen sat baseline (%)
Oxygen sat nadir (%)
Baseline study D1 D2 D3 D4
Follow-up study (when evaluating response to tx – considering closure) D5 D6 D7 D8
Most recent follow-up D9
D10
D11
D12
There are up to 3 time points where this data should be collected including: baseline, after treatment with PAH medical therapy to re-evaluate for the possibility of closure, and at most recent follow up (irrespective of whether ASD was closed).
For example, if a patient presented with an ASD-PAH, was evaluated, and put on PAH therapy – but was not a candidate for ASD closure at follow-up, the 3 time points reported would be: Baseline, Follow-up (when re-evaluation for possibility of closure occurred), and Most recent follow-up.
If a patient with ASD-PAH was evaluated, put on PAH therapy – and eventually had the ASD closed, there would be 3 time-points to report: Baseline, Follow-up (before closure), most recent follow-up (late after closure).
Section D: 6MWT
Section E: Functional class and BNP
Section F: Echocardiographic Data
Section G: Hemodynamic Data

7. Study coordinator at primary site * Assist with local IRB approval
Funding:
Gilead Investigator-Sponsored Grant (Primary IRB ), budget approved
Study coordinator at primary site *
Assist with local IRB approval
Contact point for study related questions, concerns, etc.
Communicate with participating sites
Collect and catalog case report forms
Database manager at primary site *
Compile detailed spreadsheet of collected data
Manage individual case report forms
Responsible for de-identification of sensitive information and data protection
Fiscal officer at primary site * to pay participating sites
Biostatistics Core at primary site *
Participating site reimbursement at a rate of $ per case report form (to cover time required to collect data and institutional indirect costs)
* Primary site: The Ohio State University/Nationwide Children’s Hospital

8. Timeline: Months 1--3: Enroll individual sites
Phone conference regarding design/aims/protocols
All identifying information to be de-identified at the primary site
Study coordinator to assist with dissemination of primary site IRB and work with local IRB
Local IRB approval
Months 4--9:
Individual site CRF collection
Return of CRF to primary site
Study coordinator to compile collaborating site CRFs
Months 7--12
Formalized data repository completed
Data analysis and statistical analysis
Abstract/Manuscript preparation

9. Questions…