Telemonitoring to Treat Group 2 Pulmonary Hypertension

NCT04882774 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: RECAP001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

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.

Conditions

Pulmonary Hypertension Due to Left Heart Disease

Outcome Measures

Primary Outcomes (7)

• Number of participants with normal lung impedance as measured by the ReDS vest in Ohms at Week 16

  Number of participants reaching normal lung impedance (\< 34 Ω) based on ReDS vest management.

  16 weeks

• Number of participants with normal total pulmonary resistance as measured by CardioMEMS in Woods Units at Week 16

  Number of participants reaching normal total pulmonary resistance (\< 5 Woods Units) as measured by CardioMEMS.

  16 weeks

• Number of participants reaching normal lung impedance with oral treprostinil at Week 32

  Number of participants reaching normal lung impedance (\<34 Ω) from Week 16 to Week 32 with oral treprostinil administration.

  16 weeks

• Number of participants reaching normal total pulmonary resistance with oral treprostinil at Week 32

  Number of participants reaching normal total pulmonary resistance (goal \< 5 U) from Week 16 to Week 32 with oral treprostinil administration.

  16 weeks

• Number of participants decreasing six-minute walk distance with oral treprostinil at Week 32

  Number of participants with a six-minute walk distance decrease of \>15% from Week 16 to Week 32 with oral treprostinil administration.

  16 weeks

• Number of participants maintaining normal lung impedance as measured by the ReDS vest at Week 32

  Number of participants maintaining normal lung impedance (\< 34 Ω) from Week 16 to Week 32 as measured by ReDS vest.

  16 weeks

• Number of participants maintaining total pulmonary resistance as measured by CardioMEMS at Week 32

  Number of participants maintaining normal TPR (\< 5 U) from Week 16 to Week 32 as measured by CardioMEMS.

  16 weeks

Secondary Outcomes (17)

• WHO Functional Class

  32 weeks

• Change in cardiac output

  32 weeks

• Change in cardiac index

  32 weeks

• Change in right ventricular stroke volume

  32 weeks

• Change in stroke volume index

  32 weeks

Study Arms (2)

Fluid Management

NO INTERVENTION

Fluid management protocol only

Oral Treprostinil

EXPERIMENTAL

Drug - oral treprostinil

Drug: Treprostinil Diolamine

Interventions

Treprostinil Diolamine DRUG

Oral treprostinil 0.125 mg TID titrated as clinically indicated and tolerated to a maximum of 6 mg TID

Oral Treprostinil

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Total lung capacity is ≥ 60% of the predicted value.
• Forced expiratory volume at 1 second (FEV1) is ≥50% of the predicted value.
• 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.

You may not qualify if:

• 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:
• Greater than mild aortic and/or mitral stenosis

Sponsors & Collaborators

• Mardi Gomberg -Maitland MD, MSc: lead
• Ohio State University: collaborator
• Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute): collaborator

Study Sites (3)

George Washington University

Washington D.C., District of Columbia, 20037, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Allegheny Singer Research Institute

Pittsburgh, Pennsylvania, 15212, United States

Location

MeSH Terms

Interventions

treprostinil

Study Officials

• Mardi Gomberg-Maitland, MD

  George Washington University

  PRINCIPAL INVESTIGATOR

• Raymond Benza, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Pulmonary Hypertension Program

Model Details: 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.

Study Record Dates

• First Submitted: April 27, 2021
• First Posted: May 12, 2021
• Study Start: April 1, 2023
• Primary Completion: April 1, 2025
• Study Completion (Estimated): April 1, 2027
• Last Updated: June 6, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)