Clinical trial NCT04882774: Telemonitoring to Treat Group 2 Pulmonary Hypertension
Official title: Telemonitoring to Treat Group 2 Pulmonary Hypertension: A Personalized Approach
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Pulmonary Hypertension Due to Left Heart Disease
Lead sponsor: George Washington University
Sponsor class: OTHER
Collaborators: name: Ohio State University
name: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
First posted: 2021-05-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 32 week study in 30 subjects. Those who meet certain hemodynamic criteria at Week 16 will begin study drug and continue diuresis protocol while the remaining participants continue with the diuresis protocol only.
Primary purpose: TREATMENT

Brief summary: This study aims to decrease elevated pressure in the lungs of patients with pulmonary hypertension from left heart with elevated pulmonary vascular resistance by utilizing aggressive fluid management with ReDS Pro System and CardioMEMS device. Participants with persistently elevated pulmonary pressure at Week 16 will begin oral treprostinil in combination with the fluid management plan while those with improved pressures maintain their fluid management plan for an additional 16 weeks.

Detailed description: This study hypothesizes that monitoring with ReDS-Pro System (ReDS), aggressive fluid management, and the CardioMEMS device (a 3-prong approach) will improve CpcPH (combined pre and post capillary pulmonary hypertension) hemodynamics (Total Pulmonary Resistance \[TPR\] and mPAP). For patients who continue to have an elevate pulmonary vascular resistance (TPR) at Week 16, with ReDS, aggressive fluid management, and the CardioMEMS device should allow successful titration of oral treprostinil by preventing titration related pulmonary edema and by improving hemodynamics, activity monitoring and six minute walk test (6MWT) after 16 weeks of therapy.

Eligibility criteria: Inclusion Criteria:

* The subject voluntarily gives informed consent to participate in the study.
* The subject is 18 to 85 years of age (inclusive) at Baseline (i.e., date of providing written informed consent).
* The subject has a diagnosis of heart failure with a LVEF ≥45% by ECHO completed prior to randomization.
* The subject has a CardioMEMS device implanted as standard of care for a minimum of 30 days at Baseline.
* The subject has pulmonary function tests conducted within 12 months of Baseline or to confirm the following:

  1. Total lung capacity is ≥ 60% of the predicted value.
  2. Forced expiratory volume at 1 second (FEV1) is ≥50% of the predicted value.
  3. Diffusing capacity of the lungs for carbon monoxide (DLCO) is ≥ 32% of the predicted value (unadjusted or adjusted for alveolar volume).
* Subjects should be on maximally tolerated HFpEF therapies (e.g., ACE inhibitors, ARBs, beta blockers, SLG2 inhibitors) for ≥30 days prior to enrollment unless contraindicated. The exception is with changes of anticoagulants and/or diuretics; these medications should not be newly started or stopped within 14 days of enrollment and no healthcare provider prescribed dose change should occur within 7 days of enrollment, with the exception of the withholding of doses of anticoagulants for the conduct of the RHC when required.
* In the opinion of the Investigator, the subject is able to communicate effectively with study personnel, and is considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits.
* Subjects on chronic medications (e.g. inhaled corticosteroids, long-acting beta2-adrenergic agonist, long-acting muscarinic antagonists, combination inhaled drugs, anti-inflammatory drugs, oral/parenteral corticosteroids, or biologic agents) for any underlying respiratory condition must be on a stable dose for ≥30 days prior to randomization.

Exclusion Criteria:

* The subject is pregnant or lactating.
* In the opinion of the Principal Investigator, the subject has a primary diagnosis of PH other than WHO Group 2 PH.
* The subject has shown intolerance or significant lack of efficacy to a prostacyclin or prostacyclin analogue that resulted in discontinuation of therapy or inability to effectively titrate that therapy.
* The subject has received PAH therapies, including prostacyclin therapy (i.e., epoprostenol, treprostinil, iloprost, or beraprost; except for acute vasoreactivity testing), nonprostanoid IP receptor agonist (selexipag), ERA, or soluble guanylate cyclase stimulator, within 30 days of enrollment. If the Investigator does not intend to keep a subject on their PDE5-I therapy, it must be stopped at least 30 days prior to enrollment. Intermittent use of a PDE5-I (≤3 times per week) to treat erectile dysfunction is permitted.
* The subject has been hospitalized for a cardiopulmonary indication within 30 days of randomization.
* The subject had a myocardial infarction within 90 days of enrollment.
* The subject had cardiac resynchronization therapy within 90 days of enrollment or anticipated resynchronization therapy during the study treatment period.
* The subject has liver function tests (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\]) greater than 3 times the upper limit of normal at Screening, clinically significant liver disease/dysfunction per Investigator's clinical judgement, known Child-Pugh Class C hepatic disease or noncirrhotic portal hypertension.
* The subject has uncontrolled systemic hypertension, defined as a systolic blood pressure \>160 mmHg or a diastolic blood pressure \>110 mmHg at Baseline on more than one occasion during screening.
* The subject has a systolic blood pressure \<100 mmHg at Baseline.
* The subject has a resting heart rate \>110 beats per minute at Baseline.
* The subject has sarcoidosis or cardiac amyloidosis.
* The subject has a known history of any LVEF less than 40% by ECHO within 3 years of enrollment. Note: a transient decline in LVEF below 40% that occurred and recovered more than 6 months before the start of Screening and was associated with an acute intercurrent condition (e.g., atrial fibrillation) is allowed.
* The subject has hemodynamically significant valvular heart disease as determined by the Investigator, including:

  1. Greater than mild aortic and/or mitral stenosis
  2. Severe mitral and/or aortic regurgitation (\>Grade 3)
* The subject has a body mass index \>45 kg/m2.
* The subject has any musculoskeletal disorder (e.g., arthritis affecting the lower limbs, recent hip or knee joint replacement, artificial leg), or has any other condition that would likely be the primary limit to ambulation as opposed to the disease under study.
* The subject has end-stage renal disease requiring/receiving dialysis.
* The subject has used any investigational drug/device, or participated in any investigational study, within 30 days prior to the Baseline visit.

Primary outcomes:
measure: Number of participants with normal lung impedance as measured by the ReDS vest in Ohms at Week 16
timeFrame: 16 weeks
measure: Number of participants with normal total pulmonary resistance as measured by CardioMEMS in Woods Units at Week 16
timeFrame: 16 weeks
measure: Number of participants reaching normal lung impedance with oral treprostinil at Week 32
timeFrame: 16 weeks
measure: Number of participants reaching normal total pulmonary resistance with oral treprostinil at Week 32
timeFrame: 16 weeks
measure: Number of participants decreasing six-minute walk distance with oral treprostinil at Week 32
timeFrame: 16 weeks
measure: Number of participants maintaining normal lung impedance as measured by the ReDS vest at Week 32
timeFrame: 16 weeks
measure: Number of participants maintaining total pulmonary resistance as measured by CardioMEMS at Week 32
timeFrame: 16 weeks
Secondary outcomes:
measure: WHO Functional Class
timeFrame: 32 weeks
measure: Change in cardiac output
timeFrame: 32 weeks
measure: Change in cardiac index
timeFrame: 32 weeks
measure: Change in right ventricular stroke volume
timeFrame: 32 weeks
measure: Change in stroke volume index
timeFrame: 32 weeks
measure: Change in elastance
timeFrame: 32 weeks
measure: Change in compliance
timeFrame: 32 weeks
measure: Change in right ventricular power
timeFrame: 32 weeks
measure: Change in cardiac efficiency
timeFrame: 32 weeks
measure: Change in right ventricular stroke work
timeFrame: 32 weeks
measure: Change in stroke work index
timeFrame: 32 weeks
measure: Change in NT-proBNP
timeFrame: 32 weeks
measure: Kansas City Cardiomyopathy Questionnaire
timeFrame: 32 weeks
measure: Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Questionnaire
timeFrame: 32 weeks
measure: Number of participants with heart failure exacerbation
timeFrame: 32 weeks
measure: Six-minute walk test
timeFrame: 32 weeks
measure: Number of participants who experienced mortality
timeFrame: 32 weeks
Other outcomes:
Locations:
city: Washington
country: United States
facility: George Washington University
state: District of Columbia
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny Singer Research Institute
state: Pennsylvania
Study officials:
affiliation: George Washington University
name: Mardi Gomberg-Maitland, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ohio State University
name: Raymond Benza, MD
role: PRINCIPAL_INVESTIGATOR
References: