CardioMEMSTM HF System Post Approval Study
RATIONALE: Heart failure is a major cause of morbidity and mortality. CardioMEMS HF System is an FDA approved implantable device that wirelessly measures and monitors pulmonary arterial pressure and heart rate. The CHAMPION trial demonstrated that management of heart failure using pulmonary artery pressure information obtained with the CardioMEMS HF System, in addition to traditional signs and symptoms, reduced HF hospitalizations.
INTERVENTION: Patients will be scheduled for follow-up visits at 1 month and every 6 months for 2 years. Following sensor implant and hospital discharge, subjects will take PA pressure measurements on a daily basis, or as directed by the investigator. These measurements will be automatically transmitted to the secure Patient database (CardioMEMS HF website).
OBJECTIVES: The objective of this study is to confirm the post-market safety and effectiveness of the CardioMEMS HF System to premarket.
STUDY POPULATION: Twelve hundred subjects will be enrolled with at least 35% of the enrolled patients being women (420 women out of 1200). Enrollment will be limited to 15% of the total study population at any one site.
STUDY METHODOLOGY: This is a prospective, multi-center, open-label trial conducted in the United States (US). All subjects who sign the informed consent form and satisfy the inclusion/exclusion criteria will be enrolled into the CardioMEMS HF System PAS and will be scheduled for follow-up visits at 1 month and every 6 months for 2 years. Following sensor implant and hospital discharge, subjects will take PA pressure measurements on a daily basis, or as directed by the investigator. These measurements will be automatically transmitted to the secure Patient database (CardioMEMS HF website).
STUDY ENDPOINTS:Primary safety endpoints will be evaluated at 2 years: 1) freedom from device/system related complications and 2) freedom from pressure sensor failure.
STATISTICS: The primary safety hypotheses are that the device / system-related complication-free proportion of subjects will be at least 80% at 24 months (OPC used in the CHAMPION trial) and that the pressure sensor failure-free proportion of subjects will be at least 90% at 24 months (OPC used in the CHAMPION trial). Plotting and analysis of safety endpoints will also be displayed using Kaplan-Meier methods. All safety analyses will be performed on the safety population.
AQUARESIS UTILITY FOR HYPONATREMIC ACUTE HEART FAILURE
Hyponatremia is a common finding in acute heart faiilure (HF) patients and is associated with worse prognosis. In addition to its prognostic value, hyponatremia may have importance during the acute management of HF. Weve recently shown that acute or chronic hyponatremia, especially <130 mEq/L, was associated with higher loop diuretic dose requirements and more frequent need for escalation of the diuretic regimen to achieve the same level of diuresis as normornatremic HF patients. Loop diuretics such as furosemide exert a diuretic effect through blockade of sodium reabsorption in the thick ascending limb of the Loop of Henle (natriuesis). Furosemide is the most common loop diuretic used for diuresis in HF and is an FDA approved drug. Vasopressin receptor antagonists such as tolvaptan cause diuresis through blockade of aquaporin channels in the collecting duct leading to free water elimination (aquaresis). Aquaresis with tolvaptan represents a potentially advantageous approach to the management of volume overload in HF, especially in patients presenting with concomitant hyponatremia. Tolvaptan is FDA approved for the treatment of euvolemic and hypervolemic hyponatremia (including SIADH and HF). The purpose of the current study is to prospectively evaluate the comparative efficacy and safety of a tolvaptan-based diuretic regimen compared to conventional diuresis with a furosemide-based regimen on short-term clinical and treatment outcomes in hyponatremic acute HF patients.This will be a prospective, open-label, parallel-group, randomized study comparing a tolvaptan-based aquaretic regimen to a conventional continuous infusion loop diuretic-based regimen of furosemide. Up to 50 (target sample size of 50) adult subjects admitted with acute HF and signs of volume overload, and serum sodium less than 135 mEq/L will be randomzied to tolvaptan or furosemide treatment arms (maximum of 25 subjects will be enrolled with serum sodium in the range of 130-134 mEq/L). The initial 24 hours of study treatment will compare tolvaptan monotherapy to furosemide monotherapy. After the initial 24 hours, treatment regimens may be altered to achieve desired clinical goals. Patients will be followed for up to 96 hours and at discharge for study purposes. The primary efficacy endpoint is mean urine output at 24 hours post randomization. Secondary efficacy endpoints include mean urine output at time points up to 96 hours, serum sodium changes, weight change and cumulative furosemide dose. The primary safety endpoint is mean change in serum creatinine at 24 hours post randomization. Patients will also have blood drawn to assess changes in plasma renin activity, copeptin, NT-proBNP, and cystatin C. Descriptive statistics will be computed for each treatment group. For all comparative analyses between the two treatment groups, independent samples t-test and Chi-Square test (or Fishers exact test) will be performed for continuous variables or categorical variables, respectively. If either the normality or equal-variance assumptions underlying the traditional t-tests are violated, a non-parametric test will be used.
SAFETY & EFFICACY OF INTRAMYOCARDIAL INJECTION OF MESENCHYMAL PRECURSOR CELLS ON MYOCARDIAL FUNCTION IN LVAD RECIPIENTS
This trial is being conducted within the Cardiothoracic Surgical Trials Network of which USC is a Core Clinical Site (NIH Grant 5UM1HL117924, PI Bowdish ME). The network is sponsored by the NIH, NHLBI, NINDS, Canadian Health Institute, and the Cell Therapy Network. Left ventricular assist devices (LVADS) have well-documented survival and quality of life benefits in patients with advanced heart failure for both bridge to transplantation (BTT) and as long-term therapy, so called Destination Therapy (DT) in patients who are not transplant candidates. While some LVAD recipients do recover myocardial function, the occurrence of this event is relatively rare. One method suggested to remodel or regenerate the failed myocardium and potentially allow the ability to remove the LVAD is the use of stem cells injected prior to or at the time of LVAD implantation. Recent pre-clinical and clinical evidence suggests that myocardial transplantation of allogenic mesenchymal stem cells can enhance cardiac performance in settings of acute and chronic functional impairment. The purpose of this study is to evaluate the safety and efficacy of intramyocardial injection of mesenchymal precursor cells (MPCs) on myocardial function in recipients of left ventricular assist devices. MPCs obtained from healthy donors are obtained from a commercial vendor, immunoselected, and expanded ex vivo in a Good Manufacturing Practice facility (Mesoblast, Inc.) and cryopreserved until use under an FDA IDE. The primary objectives of this trial are to evaluate the safety and efficacy of injecting MPCs (150 million dose) into the native myocardium of LVAD recipients.The secondary objectives are to explore the functional and physiologic effects of injecting MPCs (150 million dose) into the native myocardium of LVAD recipients.Patients with advanced heart failure, who are to undergo implantation of an FDA approved LVAD as either BTT or DT will be eligible to participate in the trial. The trial is multicenter. Patients will be enrolled in a single dose cohort randomized in a 2:1 allocation to intramyocardial injection of study product or control (cryoprotective media alone) at the time of LVAD implantation: - Group 1 (n=106): 150 million allogeneic MPCs (Mesoblast, Inc) - Group 2 (n=53): PlaceboA total of 159 subjects will be enrolled throughout all sites, with 6 subjects expected at USC. The primary safety endpoint is the incidence of study intervention-related adverse events (i.e., infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization).The primary efficacy endpoint is the number of temporary weans from LVAD support tolerated over 6 months following randomization. LVAD weans will be conducted at the following time points post LVAD implant: 60 & 90 days, 4, 6, 9 and 12 months (or until transplant, whichever comes first)Multiple secondary endpoints are included including all adverse events, 6 minute walk tests, ability to wean from LVAD support, physiologic and echocardiographic assessments, pathology at heart explant (if explanted for recovery or transplant), quality of life, neurocognition, length of stay, repeat hospitalizations, and resource utilization. All patients will be followed until cardiac transplantation or 24 months post randomization, whichever comes first. A Bayesian approach based on the posterior distribution that active therapy is superior to control will be used to assess the strength of potential efficacy.
Medically Ill Patient Assessment of Rivaroxaban Versus Placebo IN Reducing Post-Discharge Venous Thrombo-Embolism Risk (MARINER)
RATIONALE: The risk of developing venous thromboembolism is a major cause of morbidity in the hospitalized population. Current therapies such as heparin often have a narrow therapeutic index meaning if you don't give exactly the right doses in the therapeutic range, the patient is at risk of severe bleeding and possible mortality. Rivaroxaban is an oral, direct acting Factor Xa inihibitor anticoagulant that posseses a wider therapeutic index which reduces the risk of adverse bleeding. The rationale of this study is to compare the efficacy and safety of rivaroxaban in preventing venous thromboembolism and related deaths compared to placebo group after discharge in the high-risk medically ill population. INTERVENTION: Experiment group will receive rivaroxaban for 45 days and standard therapy. The placebo group will receive standard therapy only. OBJECTIVES: The primary objective is to assess the efficacy and safety of rivaroxaban, compared with placebo in the prevention of symptomatic VTE and VTE-related death posthospitaldischarge in high-risk, medically ill patients.STUDY POPULATION: Approximately 8000 subjects worldwide who are 40 years of age or older and hospitalized for at least 3 days with diagnoses of one of the following: congestive heart failure, acute respiratory insufficiency, acute exacerbation of chronic obstructive pulmonary disease, acute ischemic stroke, acute infectious disease, or inflammatory disease including rheumatic disease.STUDY METHODOLOGY: This is a multicenter, prospective, randomized, double-blind, placebo-controlled, event-driven study designed to evaluate rivaroxaban, compared with placebo, in the prevention of symptomatic VTE events and VTE-related deaths for a period of 45 days posthospital discharge. Study drug will start at randomization (Day 1), and will continue until Day 45 (inclusive).STUDY ENDPOINTS:The primary efficacy outcome is the composite of all symptomatic VTE events (lower extremity DVT, non-fatal PE) and VTE-related deathSTATISTICS: Key Analysis Set and Analysis Phase Intention-to-Treat (ITT): This analysis set consists of all randomized subjects who have a signed valid informed consent. Up-to-Day-45: This analysis phase includes all data from randomization to Day 45 (inclusive).