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Pilot Study to Evaluate Right Ventricular Function With Riociguat in CTEPH

Primary Purpose

Chronic Thromboembolic Pulmonary Hypertension

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Cardiac PET imaging using F-18-FDG, N-13 ammonia( NH3)
Sponsored by
Ottawa Heart Institute Research Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Chronic Thromboembolic Pulmonary Hypertension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must be able to provide their written informed consent to participate in the study after having received adequate previous information and prior to any study specific procedures.
  • At least 18 years of age at the time of screening.
  • Receiving riociguat therapy for CTEPH.
  • Patients with inoperable CTEPH or persistent or recurrent PH, after undergoing pulmonary endarterectomy.
  • CTEPH diagnosis will be based on either Ventilation/ Perfusion scan (V/Q), pulmonary angiography or computed tomography pulmonary angiography..
  • Clinical right heart catheterization performed confirming mean pulmonary artery pressure (mPAP >25 mmHg).
  • Pulmonary vascular resistance (PVR) > 300 dyne/sec/cm5

Exclusion Criteria:

  • • All types of pulmonary hypertension except Dana Point Classification Group 4 (1).

    • Patients who are currently taking Phosphodiesterase type 5 (PDE-5) inhibitors, ERAs and prostanoids ≤ 3 days prior to start of riociguat treatment.
    • Pulmonary endarterectomy surgery within 3 months of screening.
    • Epicardial coronary artery disease (Ejection Fraction <40%).
    • Previous myocardial infarction within the 3 months prior to screening.
    • Severe proven or suspected coronary artery disease (CCS Angina Classification II-IV), and/or requiring nitrates.
    • Uncontrolled arterial hypertension (systolic blood pressure> 180 mmHg and/or diastolic BP> 110 mmHg.
    • Systolic blood pressure <95mmHg.
    • Resting heart rate in an awake patient <50 beats per minute (bpm) or >105 bpm.
    • History of uncontrolled atrial fibrillation within the last 3 months prior to screening.
    • Hypertrophic obstructive cardiomyopathy.
    • Clinical evidence of symptomatic atherosclerotic disease (peripheral artery disease).
    • Pregnant or breastfeeding women or women with childbearing potential not using highly effective contraception methods.
    • Renal insufficiency (glomerular filtration rate < 30 ml/min.
    • ALT or AST > times upper limit of normal( ULN) and/or severe hepatic insufficiency.
    • Contraindication to MRI imaging.

Sites / Locations

  • University of Ottawa Heart Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Riociguat therapy

Arm Description

After an overnight fast, patients will undergo a 20 minute dynamic PET scan with injection of 3 MBq/kg of N-13 ammonia (NH3) to measure myocardial perfusion. Followed by a 60 min dynamic PET scan with injection of 3MBq/kg of F-18-FDG to measure glucose uptake.

Outcomes

Primary Outcome Measures

Evidence of changes in glucose metabolism and myocardial RV blood flow in patients treated with riociguat using PET imaging.
Subjects will undergo FDG (fluorodeoxyglucose, F-18)cardiac positron emission tomography studies (PET) at baseline and 24 weeks to assess regional myocardial blood flow. The assessment of regional myocardial blood flow will be combined with 3D echocardiography and magnetic resonance (MR)

Secondary Outcome Measures

Evidence of improved RV function and volumes using 3D echocardiography and magnetic resonance imagining (MRI)
The assessment of will be obtained by 3D echocardiography and MRI to evaluate RV function.

Full Information

First Posted
March 17, 2014
Last Updated
August 28, 2018
Sponsor
Ottawa Heart Institute Research Corporation
Collaborators
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT02094001
Brief Title
Pilot Study to Evaluate Right Ventricular Function With Riociguat in CTEPH
Official Title
Evaluation of Right Ventricular Function and Metabolism Following Riociguat for the Treatment of Chronic Thromboembolic Pulmonary Hypertension- Images of Rio
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
May 2014 (Actual)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ottawa Heart Institute Research Corporation
Collaborators
Bayer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Chronic thromboembolic Pulmonary hypertension(CTEPH) is characterized by obstruction of the pulmonary vasculature, leading to increased pulmonary vascular resistance, progressive pulmonary hypertension (PH) and right ventricular failure- most common cause of death for patients with PH. Riociguat, (ADEMPAS) is a member of a new class of drug recently approved in Canada for the treatment of CTEPH. This pilot study is designed to assess if at least 24 weeks of treatment with riociguat will show changes in glucose metabolism and improved resting myocardial blood flow using positron emission tomography ( PET ) imaging to measure myocardial function. The response between both treatment naive patients as well as patients on maximally tolerated dose of riociguat with tratment duration of at least 3 months will be included.
Detailed Description
It remains unclear as to why certain patients with PH develop right heart failure. Several lines of evidence suggests alterations in right ventricular (RV) function may be precipitated by RV ischemia. This ischemia results from both decreased right coronary artery perfusion pressure and from arteriolar- capillary rarefaction. It has been proposed that this contributes to insufficient oxygen delivery needed to support the increase RV demand in right heart failure (RHF), this stimulating glycolytic shift. However, this glycolysis is insufficient to compensate for suppression of glucose oxidation in severe right ventricular hypertrophy (RVH), resulting in a state of RV hibernation and progressive RHF. This study is designed to assess if 24 weeks of treatment with riociguat will be associated with changes in glucose metabolism and improved RV blood flow using N-13-ammonia (NH3) to measure myocardial perfusion. We will assess the response in both treatment naive patients as well as patients who have been titrated to maximally tolerated doses of riociguat with total treatment duration of at least 3 months. The assessment of quantitative myocardial blood flow will be combined with an advanced 3 dimensional echocardiographic assessment of RV volume and function and with cardiac magnetic resonance (MR).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Thromboembolic Pulmonary Hypertension

7. Study Design

Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Riociguat therapy
Arm Type
Experimental
Arm Description
After an overnight fast, patients will undergo a 20 minute dynamic PET scan with injection of 3 MBq/kg of N-13 ammonia (NH3) to measure myocardial perfusion. Followed by a 60 min dynamic PET scan with injection of 3MBq/kg of F-18-FDG to measure glucose uptake.
Intervention Type
Radiation
Intervention Name(s)
Cardiac PET imaging using F-18-FDG, N-13 ammonia( NH3)
Intervention Description
After an overnight fast, patients will undergo a 20 minute dynamic PET scan with injection of 3 MBq/kg of N-13 ammonia (NH3) to measure myocardial perfusion. Followed by a 60 min dynamic PET scan with injection of 3MBq/kg of F-18-FDG to measure glucose uptake.
Primary Outcome Measure Information:
Title
Evidence of changes in glucose metabolism and myocardial RV blood flow in patients treated with riociguat using PET imaging.
Description
Subjects will undergo FDG (fluorodeoxyglucose, F-18)cardiac positron emission tomography studies (PET) at baseline and 24 weeks to assess regional myocardial blood flow. The assessment of regional myocardial blood flow will be combined with 3D echocardiography and magnetic resonance (MR)
Time Frame
After 24 weeks of treatment with riociguat.
Secondary Outcome Measure Information:
Title
Evidence of improved RV function and volumes using 3D echocardiography and magnetic resonance imagining (MRI)
Description
The assessment of will be obtained by 3D echocardiography and MRI to evaluate RV function.
Time Frame
baseline and 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must be able to provide their written informed consent to participate in the study after having received adequate previous information and prior to any study specific procedures. At least 18 years of age at the time of screening. Receiving riociguat therapy for CTEPH. Patients with inoperable CTEPH or persistent or recurrent PH, after undergoing pulmonary endarterectomy. CTEPH diagnosis will be based on either Ventilation/ Perfusion scan (V/Q), pulmonary angiography or computed tomography pulmonary angiography.. Clinical right heart catheterization performed confirming mean pulmonary artery pressure (mPAP >25 mmHg). Pulmonary vascular resistance (PVR) > 300 dyne/sec/cm5 Exclusion Criteria: • All types of pulmonary hypertension except Dana Point Classification Group 4 (1). Patients who are currently taking Phosphodiesterase type 5 (PDE-5) inhibitors, ERAs and prostanoids ≤ 3 days prior to start of riociguat treatment. Pulmonary endarterectomy surgery within 3 months of screening. Epicardial coronary artery disease (Ejection Fraction <40%). Previous myocardial infarction within the 3 months prior to screening. Severe proven or suspected coronary artery disease (CCS Angina Classification II-IV), and/or requiring nitrates. Uncontrolled arterial hypertension (systolic blood pressure> 180 mmHg and/or diastolic BP> 110 mmHg. Systolic blood pressure <95mmHg. Resting heart rate in an awake patient <50 beats per minute (bpm) or >105 bpm. History of uncontrolled atrial fibrillation within the last 3 months prior to screening. Hypertrophic obstructive cardiomyopathy. Clinical evidence of symptomatic atherosclerotic disease (peripheral artery disease). Pregnant or breastfeeding women or women with childbearing potential not using highly effective contraception methods. Renal insufficiency (glomerular filtration rate < 30 ml/min. ALT or AST > times upper limit of normal( ULN) and/or severe hepatic insufficiency. Contraindication to MRI imaging.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lisa M Mielniczuk, MD
Organizational Affiliation
Ottawa Heart Institute Research Corporation
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Ottawa Heart Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y4W7
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

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Pilot Study to Evaluate Right Ventricular Function With Riociguat in CTEPH

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