Cardiology: Clinical Research Program

Inclusion Criteria 

• Is an adult male or female patient ≥ 18 years of age (or adult age as per country guidelines) and ≤ 85 years of age at the time of screening.
• Is able to understand and willing to comply with all trial procedures through the duration of planned follow-up, understand the risks involved in the trial, and provide written informed consent.
• Has a medical history supporting a diagnosis of clinical chronic HF syndrome with a duration of at least 8 weeks prior to the time of screening and current NYHA functional class II to III (based on investigator’s assessment).
• Has left ventricular EF ≤ 40% by a centrally read TTE performed during screening.
• Has NT-proBNP level ≥ 600 pg/mL (70.8 pmol/L) at the time of screening. Patients in atrial fibrillation or flutter at the time of screening are required to have an NT-proBNP level of ≥ 900 pg/mL (106.4 pmol/L).
• Is receiving optimized and stable guideline directed HF therapy (per applicable regional or national guidelines). Stable therapy is defined as having no new drug class introduced within 8 weeks prior to the time of screening or during screening (including intravenous iron replacement), and stable optimized doses for a minimum of 4 weeks prior to and during screening (excluding diuretics).

Exclusion Criteria 

• Inadequate acoustic windows based on echocardiography core laboratory assessment of screening echocardiogram.
• Has evidence of recent HF exacerbation defined by hospitalization or requirement for IV or SQ diuretics within 4 weeks of the time of screening or during the Screening Period.
• Has a requirement for routine, scheduled outpatient IV infusions for HF (ie, inotropes, vasodilators, or diuretics) or routinely scheduled ultrafiltration. Repeat administration of IV iron replacement is allowed as clinically indicated per the investigator’s judgment but the initiation of IV iron replacement must be > 8 weeks prior to screening.
• Has QTc (Fridericia formula), corrected for QRS if applicable, ≥ 450 ms at screening. To evaluate eligibility, the QT will be corrected for a widened QRS using the formula provided in Section 8.4.3.1.
• Has a known family history of a first-degree relative with long QT syndrome.
• Current chronic treatment with a Vaughn Williams Class I or III antiarrhythmic drug.
• Recent initiation (< 2 weeks prior to screening) of any medication that is known to cause prolongation of the QT interval.
• Has laboratory evidence at screening of untreated hypothyroidism, defined as serum TSH level above the upper limit of normal.
• Has electrolyte imbalances defined as serum potassium, albumin-corrected serum calcium, or serum magnesium levels below the lower limit of normal at screening.
• Has any elective invasive interventions (eg percutaneous coronary intervention, de novo device implantations, percutaneous structural heart disease interventions, or major cardiac or non-cardiac surgery) planned to occur during trial participation or has undergone this elective procedure within 8 weeks prior to screening, or during the Screening Period.
• Has acute coronary syndrome, unstable angina, persistent angina at rest, stroke, transient ischemic attack, cardiac, carotid or other major cardiovascular surgery, cardiac valve repair (surgical or nonsurgical) or surgical replacement, or carotid angioplasty within 8 weeks prior to screening or during the Screening Period.
• Has clinical suspicion of infiltrative cardiomyopathy (eg, amyloid, sarcoid), hypertrophic cardiomyopathy (obstructive or non-obstructive), or HF secondary to severe valvular disease, active myocarditis, active pericarditis, or clinically significant congenital heart disease.
• Has had a prior or planned orthotopic heart transplantation (being on a transplant list is acceptable as long as the investigator does not anticipate a transplant within the next year).
• Has presence of or plan for mechanical circulatory support.
• Has known bleeding diathesis.

Enrollment Status: Open to Enrollment

Study Information: NCT06658899

Principal Investigator: Stephen Pan, MD

Contact for Study Screening: [email protected]

Inclusion Criteria 

1. Is an adult male or female patient ≥ 18 years of age
2. Informed consent obtained and signed before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
3. Body Mass Index (BMI) ≥ 30 kg/m2 at screening.
4. Diagnosis of heart failure with New York Heart Association (NYHA) class II-IV and in stable condition at screening, at the discretion of the investigator.
5. Cardiac dysfunction with LVEF > 40%b documented by echocardiography (within 12 months prior to or at screening), cardiac magnetic resonance imaging (MRI) or computed tomography (CT) within 12 months prior to screening (V1/V1B). The LVEF must be documented in medical records and the most recent measurement must be used to determine eligibility with no interim event signalling potential deterioration in ejection fraction (e.g., MI or HF hospitalisation).
6. Evidence of increased filling pressure or structural changes with at least one of the following criteria based on 1) most recent examination within 12 months before or at screening (preferably determined by echocardiography (at screening), alternatively cardiac CT or MRI), or 2) most recent invasive testing within 12 months before screening:

• Septal é < 7 cm/sec or lateral é < 10 cm/sec
• Average E/é ≥ 10
• Pulmonary artery systolic pressure > 35 mmHg
• Left atrial (LA) enlargement (LA width ≥ 3.8 cm or LA length ≥ 5 cm)
• LA area ≥ 20 cm2
• LA volume ≥ 55 mL
• LA volume index > 34 mL/m2
• Left ventricular (LV) mass index ≥115 g⁄m2 in men or ≥ 95 g⁄m2 in women
• Septal thickness or posterior wall thickness ≥ 1.1 cm (women) or ≥ 1.2 cm (men)
• Mean pulmonary wedge pressure ≥ 15 mmHg or left ventricular end diastolic pressure (LVEDP) ≥ 15 mmHg documented during catheterisation at rest
• Mean pulmonary wedge pressure or LVEDP ≥ 25 mmHg documented during catheterisation at exercise
• Pulmonary artery diastolic pressure measured by implantable monitor ≥ 15 mmHg

7. Elevated NT-proBNP in relation to BMI as measured by the central laboratory at screening:

• BMI < 35 kg/m2: NT-proBNP ≥ 150 pg/mL (≥ 300 pg/mL if in atrial fibrillation/flutter)
• BMI ≥ 35 kg/m2: NT-proBNP ≥ 100 pg/mL (≥ 200 pg/mL if in atrial fibrillation/flutter)

8. At least one of the following at screening:

1. HF decompensation within 12 months of screening, documented by one of the following with a primary diagnosis of decompensated HF:

• Hospitalisation
• Urgent or unplanned visit requiring intravenous loop diuretic treatment

1. Estimated glomerular filtration rate (eGFR; based on the creatinine value using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] 2021 equation) < 60 mL/min/1.73m2 prior to screening
2. Urine albumin-to-creatinine ratio (UACR) > 30 mg/g

For participants with T2D at screening:

9. Diagnosed with T2D ≥ 30 days before screening.
10. Treated with diet, exercise and/or glucose lowering agent(s) according to local label in stable dosing for at least 30 days before screening.

Exclusion Criteria 

1. Myocardial infarction (MI), stroke, unstable angina pectoris or worsening HF leading to either hospitalization or intravenous loop diuretics within 30 days prior to the day of screening and until randomization.
2. Any of the below:
3. Coronary, carotid, or peripheral artery revascularization or percutaneous valve repair or replacement (e.g. TAVI, mitraclip) planned during the study period and known at screening (V1).
4. HF due to infiltrative cardiomyopathy (e.g., sarcoid, amyloid), arrhythmogenic right ventricular cardiomyopathy, Takutsubo cardiomyopathy, Chagas cardiomyopathy, genetic hypertrophic cardiomyopathy or obstructive cardiomyopathy or presence of pathogenic/likely pathogenic hypertrophic cardiomyopathy variant, active myocarditis, constrictive pericarditis, cardiac tamponade, or uncorrected primary valve disease of moderate or severe degree.
5. Severe pulmonary disease including primary pulmonary hypertension, chronic pulmonary embolism, or severe chronic obstructive pulmonary disease (COPD) defined as: requiring home oxygen; or ongoing oral corticosteroid therapy; or hospitalised for COPD exacerbation within 12 months prior to screening
6. Any other condition judged by the investigator to be the cause of HF symptoms (e.g. anaemia, hypothyroidism.)

Enrollment Status: Open to Enrollment

Study Information: NCT07567001

Principal Investigator: Stephen Pan, MD

Contact for Study Screening: [email protected]

Eligibility

• Male or female, 22-85 years of age.
• Documented history of symptomatic or asymptomatic paroxysmal or persistent AF. The duration of AF must have been > 30 seconds as documented by an external monitor or present on 12-lead ECG.
• CHA2DS2-VASC score of 1-4 without prior stroke or TIA**
• The participant is on a DOAC at the time of screening.
• Inclusion/Exclusion Criteria: for matched healthy controls; Valvular or permanent atrial fibrillation, Current treatment with warfarin and unwilling or unable to take a DOAC.

Enrollment Status: Actively enrolling

Study Information

Grant # UG3HL15065

Principal Investigator

Jason Jacobson, MD

Contact for Study Screening

[email protected] or [email protected]

Eligibility

• Subjects diagnosed with persistent (not longstanding) AF or recurrent AF, as defined for this study.
• Subject has a recent 12-lead electrogram data of AF (including baseline, pacing and clinical arrhythmia) recorded on the electrogram recording system (e.g., Bard, Boston-Scientific, St. Paul, MN or Prucka, GE Medical) or standalone ECG system (e.g., GE Muse, Minnesota, or CardioCard (Nasiff, NY) in digitized format.
• The following data elements can be abstracted from the patient medical records or confirmed and documented prior to the scheduled procedure (to be inputted in vMap®):
  • Atrial fibrillation type
  • Atrial characteristics: geometry (normal, left and/or right atrial enlargement), Utah classification, prior ablation modality (e.g., radiofrequency, cryoablation, pulsed field ablation), prior ablation lesion location(s).
• Subject is ≥ 22 years of age at time of enrollment/consent.
• Subject is indicated to undergo an ablation procedure at the medical discretion of the Investigator.
• Subject is able and willing to comply with the protocol requirements, has been informed of the nature of the study.
• Exclusion Criteria:
  • Subjects with arrhythmias other than persistent or recurring AF as defined for this study, including long-standing persistent atrial fibrillation (persistent AF lasting ≥ 1 year from diagnosis).
  • Inability to obtain ECG prior to or during the clinical ablation procedure; or unacceptable ECG data quality such as low ECG signal-to-noise ratio or lack of ECG data in one or more leads.
  • Subjects who are participating in another clinical investigation with an investigational drug or device at the time of enrollment or planned participation at any time during this clinical investigation.
  • Subjects who have a known or suspected medical condition that, in the opinion of the Investigator, may put the subject at risk for participation in this clinical investigation.
  • Subjects who are pregnant as confirmed by the institution’s standard pre-surgery practice.

Enrollment Status: Actively enrolling

Study Information

ClinicalTrials.gov | NCT06935591

Principal Investigator

Sei Iwai, MD

Contact for Study Screening

[email protected]

Eligibility

• Males or females age >18
• Presence of BIV pacemaker or defibrillator
• Exclusion Criteria:
  • Unable or unwilling to provide consent
  • Non-English-speaking patients

Enrollment Status: Actively enrolling

Principal Investigator

Jason Jacobson, MD

Contact for Study Screening

[email protected]

Eligibility

• Men and women 18 and 75 years of age (inclusive) at the time of signing the ICF.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• Documented diagnosis of WHO PAH Group 1 in any of the following subtypes:
  • Idiopathic PAH
  • Heritable PAH
  • Drug/toxin-induced PAH
  • PAH associated with CTD
  • PAH associated with simple, congenital systemic-to-pulmonary shunts ≥1 year following repair
• Must have a BMI of ≥18.5 kg/m2 and ≤35.0 kg/m2 during screening.
• Baseline RHC performed during the screening period documenting a PVR of ≥400 dyn·sec·cm-5, a PCWP or left ventricular end-diastolic pressure of ≤15 mmHg, and an mPAP of >20 mmHg. If the population mean baseline PVR falls below 700 dyn·sec·cm-5, enrollment may be restricted to participants with a baseline PVR of ≥600 dyn·sec·cm-5 for the remainder of the study.
• On stable doses of background PAH therapy (≤3 PAH specific medications) including endothelin receptor antagonists, phosphodiesterase-5 inhibitors, prostacyclins, and soluble guanylate cyclase stimulators for ≥90 days before screening. Current use of sotatercept is not permitted in this study.
• Anticipated to be able to perform the 6MWT according to American Thoracic Society Guidelines for the duration of the study.
• 6MWD ≥100 and ≤475 m repeated twice at screening (measured at least 4 hours but no longer than 1 week apart), with both values within 15% of each other (calculated from the highest value).
• NT-proBNP >300 ng/L during screening.
• If female and a WOCBP as defined in Section 7.2.1, must meet all the requirements below:
  • Agrees to use a contraceptive method that is highly effective (defined as having a failure rate of <1% per year as described in Section 7.2.2) from 30 days before dosing through 14 days after the last dose of study drug AND
  • Agrees not to donate eggs (ova, oocytes) for the purpose of reproduction from at least 14 days prior to dosing through the end of the study AND
  • Has negative pregnancy tests at screening and before the administration of the first dose of study drug
• Exclusion Criteria:
  • Diagnosis of PAH WHO Groups 2, 3, 4, or 5.
  • Diagnosis of the following PAH Group 1 subtypes:
    • HIV-associated PAH
    • PAH associated with portal hypertension
    • Schistosomiasis-associated PAH
    • Pulmonary veno-occlusive disease
  • Diagnosis or history of any of the following substance-related conditions:
    • Methamphetamine-associated PAH
    • History of cocaine or methamphetamine (amphetamine-type stimulant) use within 24 months prior to screening defined by self-report, medical history, or positive drug screen in medical records
    • Any diagnosis of cocaine or methamphetamine use disorder (per medical record or self-report) within 24 months prior to screening
  • Uncontrolled diabetes mellitus, defined as HbA1c ≥9.0%.
  • Any of the following BP-related values or abnormalities:
    • Uncontrolled systemic hypertension as evidenced by sitting systolic BP >160 mmHg or sitting diastolic BP >100 mmHg at screening after 5 minutes of rest
    • Baseline systolic BP <90 mmHg at screening
    • Syncope within 3 months before screening
  • History of restrictive, constrictive, or congestive cardiomyopathy.
  • ECG with QTcF ≥450 msec in males or ≥470 msec in females at screening or ≥500 msec in the presence of a right bundle branch block.
  • Personal or family history of long QT syndrome or sudden cardiac death.
  • Presence of a CardioMEMS device or any other implanted hemodynamic monitoring device.
  • FVC <70% on PFT performed no more than 6 months before screening; or if FVC is 60% to 69%, must have a chest computed tomography scan within 12 months with no more than mild interstitial lung disease.
  • Evidence of LVEF <45% (by Simpson’s biplane method) or evidence of impaired relaxation on screening echocardiogram by E/e’ >13.
  • History of atrial fibrillation or atrial flutter.

Enrollment Status: Enrolling

Study Information

ClinicalTrials.gov | NCT07365332

Principal Investigator

Erika Berman-Rosenzweig, MD

Contact for Study Screening

[email protected]