Non-Invasive Measurement of Cardiac Output and Stroke Volume in PAH/CTEPH

Pulmonary Arterial Hypertension Clinical Trial

Official title:

Use of Non-invasive Measurement of Cardiac Output and Stroke Volume to Assess Risk and Response to Treatment in Patients With PAH or CTEPH

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05618093
• Other study ID #: 20-001981
• Status: Enrolling by invitation
• Phase: N/A
• Start date: March 2, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2023
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are severe clinical conditions that, despite advances in therapeutics over the past 20 years, lead to serious morbidity and mortality. Guidelines on the diagnosis and treatment of pulmonary hypertension (PH) recommend the use of a multiparametric risk stratification tool to determine severity of disease, which should guide initial therapy and therapy modulation. This multiparametric risk stratification schema includes objective assessment of exercise capacity, right ventricular function and hemodynamic parameters in order to classify patients into severity categories. Cardiac index (CI) and right atrial pressure (RAP), measured via right heart catheterization (RHC), are the hemodynamic parameters used in risk assessment of PH. Arguably, stroke volume index (SVI) is the most important hemodynamic parameter for assessment of PH severity and there is currently no validated method for noninvasive measurement of cardiac output (CO), CI or SVI. Currently, a major obstacle in the field is that hemodynamic measurements are not obtained on a regular basis in the risk assessment and therapy modulation of patients with PAH and CTEPH. If a noninvasive method of hemodynamic measurement could be correlated with other objective measurements of risk assessment, it could become an invaluable tool in therapy initiation and modulation in the ambulatory setting.

This is a single center study to evaluate the use of non-invasive measurement of CO and stroke volume to assess risk and response to treatment in patients with PAH and non- operable CTEPH. We anticipate to enroll a total of 100 subjects at Ronald Reagan UCLA Medical Center.

A maximum of 10 hour in total for the study including the consent process, pre-procedure care, RHC procedure, and follow up visit. The initial visit will be approximately 4 hours with the RHC procedure itself will only be 20 minutes. Each follow up visit will be 1.5 hour.

Patients with known or suspected PAH or CTEPH will undergo a RHC as part of his or her standard of care. Three techniques of CO measurement will be performed sequentially at the time of the RHC.

The device that will be used is the Edwards ClearSight system and EV1000 clinical platform, a device that measures NIBP.

Patients will be followed over the period of 1 year every 3 months to obtain serial measurements for six-minute walk distance (6MWD), World Health Organization (WHO)/New York Heart Association Functional Class (FC), B-type natriuretic peptide (BNP) or N-terminal-pro hormone BNP (NT-proBNP), and non-invasive hemodynamic measurements. Additional visits will be scheduled to obtain the serial measurements one month prior and one month following if a patient is initiating or changing PH-specific therapy.

As this is a study looking at the feasibility of non-invasive measurement of cardiac output and stroke volume for risk assessment and response to therapy in pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH), study personnel performing the study procedures will not be blinded to the clinical diagnosis and the management of the subject.

Description:

This is a single center study to evaluate the use of non-invasive measurement of cardiac output and stroke volume to assess risk and response to treatment in patients with pulmonary arterial hypertension (PAH) and non- operable chronic thromboembolic pulmonary hypertension (CTEPH). We anticipate to enroll a total of 100 subjects at Ronald Reagan UCLA Medical Center.

After informed consent is obtained, the following procedure will be performed:

Patients with known or suspected pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) will undergo a right heart catheterization (RHC) as part of his or her standard of care. Three techniques of cardiac output (CO) measurement will be performed sequentially at the time of the RHC. The order of cardiac output testing will be randomized after informed consent is obtained and prior to the procedure. The operator performing the RHC procedure will be blinded to both the non-invasive blood pressure (NIBP) measurement and direct Fick cardiac output (CO) measurements while performing thermodilution cardiac output (CO) measurement.

The device that will be used is the Edwards ClearSight system and EV1000 clinical platform, a device that measures non-invasive blood pressure (NIBP).

Patients will be followed over the period of 1 year, up to every 3 months, to obtain serial measurements of six-minute walk distance (6MWD), World Health Organization (WHO)/New York Heart Association Functional Class (FC), and B-type natriuretic peptide (BNP) or N-terminal-pro hormone BNP (NT-proBNP) as part of standard of care. These serial measurements will be collected from the patient's medical record. Non-invasive hemodynamic measurements will be performed for research purposes. Additional visits will be scheduled to obtain the serial measurements one month prior and one month following if a patient is initiating or changing PH-specific therapy.

As this is a study looking at the feasibility of non-invasive measurement of cardiac output and stroke volume for risk assessment and response to therapy in pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH), study personnel performing the study procedures will not be blinded to the clinical diagnosis and the management of the subject.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 100
• Est. completion date: December 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient = 18 years of age.

• The patient must understand and sign informed consent form (ICF).

• Patients with a confirmed diagnosis or suspected diagnosis of pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) prior to initiation or change in therapy.

• PAH or CTEPH patients undergoing right heart catheterization (RHC) as part of their standard of care.

Exclusion Criteria:

• BMI < 20 or BMI > 35.

• Height less than 120 cm.

• Diagnosis of atrial fibrillation, aortic or mitral valve insufficiency or stenosis, or end-stage renal disease.

Related Conditions & MeSH terms

• Chronic Thromboembolic Pulmonary Hypertension
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Arterial Hypertension

Intervention

Device:
• Non-invasive hemodynamic measurements
A patient profile will be set up in the Edwards EV1000 clinical platform by inputting the patient's demographic information. One or two Edwards ClearSight finger cuffs will be placed on the index, middle, and/or ring finger on one hand of the patient. A pressure controller will be secured by a forearm strap where the finger cuffs will be connected to the pressure controller. The pressure controller will be connected to the Edwards EV1000 clinical platform monitor. A heart reference sensor (HRS) will be connected to the pressure controller, a finger cuff, and to the patient at heart level. The Edwards EV1000 clinical platform will calibrate the finger probes, then record measurements for 10-30 seconds. If two finger probes are available, measurements will alternate between fingers.

Locations

Country	Name	City	State
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (27)

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* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	stroke volume (SV)	Stroke Volume (SV) is the volume of blood in millilitres ejected from the each ventricle due to the contraction of the heart muscle which compresses these ventricles.	12 months
Primary	stroke volume index (SVI)	Stroke Volume Index (SVI) relates SV to body surface area (BSA), thus relating heart performance to the size of the individual. The unit of measurement is millilitres per square metre (ml/m2).	12 months
Primary	cardiac output (CO)	Cardiac Output (CO) is the amount of blood the heart pumps from each ventricle per minute. It is usually expressed in litres per minute (L/min).	12 months
Primary	cardiac index (CI)	Cardiac index (CI) is the cardiac output proportional to the body surface area (BSA). The unit of measurement is litres per minute per square metre (L/min/m2).	12 months
Primary	systemic vascular resistance (SVR)	Systemic vascular resistance (SVR) refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature.; The units for SVR are most commonly expressed as pressure (mmHg) divided by cardiac output (mL/min), or mmHg·min·mL^-1	12 months
Primary	blood pressure (BP)	The pressure of the blood in the circulatory system, often measured for diagnosis since it is closely related to the force and rate of the heartbeat and the diameter and elasticity of the arterial walls.; Systolic Blood Pressure in mmHg Diastolic Blood Pressure in mmHg	12 months
Primary	heart rate (HR)	The number of heartbeats per unit of time, usually per minute.; Measured in beats per minute (BPM)	12 months
Secondary	six-minute walk distance (6MWD)	The distance covered over a time of 6 minutes. This is used as the outcome by which to compare changes in performance capacity.	12 months
Secondary	B-type natriuretic peptide (BNP) or N-terminal-pro hormone BNP (NT-proBNP)	B-type natriuretic peptide (BNP) is a hormone produced by your heart. N-terminal (NT)-pro hormone BNP (NT-proBNP) is a non-active prohormone that is released from the same molecule that produces BNP. Both BNP and NT-proBNP are released in response to changes in pressure inside the heart. These changes can be related to heart failure and other cardiac problems. Levels goes up when heart failure develops or gets worse, and levels goes down when heart failure is stable.	12 months
Secondary	World Health Organization (WHO)/New York Heart Association Functional Class (FC)	The World Health Organization functional classification (WHO-FC) is a tool used to measure disease severity in patients with PAH whereby health care providers (HCPs) use patient reports of symptom experience and activity limitations to make their assessment.	12 months