Tadalafil and Nesiritide as Therapy in Pre-clinical Heart Failure

• Status: Completed
• Trial end date: 2014-08-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is being done to determine the effects of subcutaneous (under the skin) injection of human B-type natriuretic factor (BNP), Natrecor (nesiritide), a hormone produced by the heart, in combination with Tadalafil on:

• The pumping function of the heart

• Kidney function

• Hormonal function (levels of different hormones in your blood) in persons with lower pumping function of their heart.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mayo Clinic
• Collaborators: National Center for Research Resources (NCRR); National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Natriuretic Peptide, Brain; Tadalafil

Criteria

Inclusion Criteria:

Group 1 (PSD)

• an ejection fraction of less than 45% with no clinical signs or symptoms of congestive heart failure;

• a minimal distance on 6-minute walk of >450 meters

• calculated creatinine clearance of equal or less than 90 ml/min and greater than 30 ml/min, using the Modification of Diet in Renal Disease (MDRD) formula assessed within the past 24 months. If the creatinine clearance is > 24 months a creatinine test can be drawn at screen/enrollment visit.

• A 6-minute walk distance of 450 meters

Group 2 (PDD)

• ejection fraction of greater than 50% with moderate or severe diastolic dysfunction as assessed by Doppler echocardiography,

• who do not have any signs or symptoms of congestive heart failure

• minimal distance on 6-minute walk of >450 meters

• calculated creatinine clearance of equal or less than 90 ml/min and greater than 30 ml/min

Exclusion Criteria:

• Current or anticipated future need for nitrate therapy

• Systolic blood pressure < 90 mmHg or > 180 mm Hg

• Diastolic blood pressure < 40 mmHg or > 100 mmHg

• Resting heart rate (HR) > 100 bpm

• Patients taking alpha antagonists or cytochrome P450 3A4 inhibitors (ketoconazole, itraconazole, erythromycin, saquinavir, cimetidine or serum protease inhibitors for HIV).

• Patients with retinitis pigmentosa, previous diagnosis of nonischemic optic neuropathy, untreated proliferative retinopathy or unexplained visual disturbance

• Patients with sickle cell anemia, multiple myeloma, leukemia or penile deformities placing them at risk for priapism (angulation, cavernosal fibrosis or Peyronie's disease)

• Contraindication to nesiritide.

• Patients with an allergy to iodine.

• Valve disease (> moderate aortic or mitral stenosis; > moderate aortic or mitral regurgitation)

• Hypertrophic cardiomyopathy

• Infiltrative or inflammatory myocardial disease (amyloid, sarcoid)

• Pericardial disease

• Have experienced a myocardial infarction or unstable angina, or have undergone percutaneous transluminal coronary angiography (PTCA) or coronary artery bypass grafting (CABG) within 60 days prior to consent, or requires either PTCA or CABG at the time of consent

• Severe congenital heart diseases

• Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening

• Second or third degree heart block without a permanent cardiac pacemaker

• Stroke within 3 months of screening or other evidence of significantly compromised central nervous system (CNS) perfusion

• Patients with severe liver disease (AST > 3x normal, alkaline or bilirubin > 2x normal)

• Serum sodium of < 125 milliequivalents (mEq)/dL or > 150 mEq/dL

• Serum potassium of < 3.2 mEq/dL or > 5.7 mEq/dL

• Prior diagnosis of intrinsic renal diseases including renal artery stenosis of > 50%

• Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period

• Less than 21 years of age

• Pregnant or nursing women.

• Women of child bearing potential who do not have a negative pregnancy test at study entry and who are not using effective contraception