Pilot Study to Evaluate Right Ventricular Function With Riociguat in CTEPH

NCT02094001 | Completed Phase 2

• 1 other identifier: 20130903-01H
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Thromboembolic Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• 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)

  After 24 weeks of treatment with riociguat.

Secondary Outcomes (1)

• Evidence of improved RV function and volumes using 3D echocardiography and magnetic resonance imagining (MRI)

  baseline and 24 weeks

Study Arms (1)

Riociguat therapy

EXPERIMENTAL

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.

Radiation: Cardiac PET imaging using F-18-FDG, N-13 ammonia( NH3)

Interventions

Cardiac PET imaging using F-18-FDG, N-13 ammonia( NH3) RADIATION

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.

Riociguat therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ottawa Heart Institute Research Corporation: lead
• Bayer: collaborator

Study Sites (1)

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y4W7, Canada

Location

Study Officials

• Lisa M Mielniczuk, MD

  Ottawa Heart Institute Research Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Pulmonary Hypertension Clinic

Study Record Dates

• First Submitted: March 17, 2014
• First Posted: March 21, 2014
• Study Start: May 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: August 29, 2018

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)