TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases.

Purpose: Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer to the CNS are limited. We previously reported modest activity of neratinib monotherapy for HER2-positive breast cancer brain metastases. Here we report the results from additional study cohorts.

Enhancing clinical trial development for pediatric kidney diseases.

The conduct of clinical trials in small pediatric subspecialties such as pediatric nephrology is hampered by both clinical demands on the pediatric nephrologist and the small number of appropriate patients available for such studies. The American Society of Pediatric Nephrology Therapeutics Development Committee (TDC) was established to (1) identify the various stakeholders with interests and/or expertise related to clinical trials in children with kidney disease and (2) develop more effective partnerships among all parties regarding strategies for successful clinical trial development and execution. This article discusses the rationale, structure, and function of the TDC, the status of progress toward its goals, and the insights gained to date that may be useful for other subspecialties that face similar challenges.

Results of bococizumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9, from a randomized, placebo-controlled, dose-ranging study in statin-treated subjects with hypercholesterolemia.

Bococizumab is a humanized monoclonal antibody binding proprotein convertase subtilisin/kexin type 9, which may be a potential therapeutic option for reducing low-density lipoprotein cholesterol (LDL-C) levels in patients with hypercholesterolemia. In this 24-week, multicenter, double-blind, placebo-controlled, dose-ranging study (NCT01592240), subjects with LDL-C levels≥80 mg/dl on stable statin therapy were randomized to Q14 days subcutaneous placebo or bococizumab 50, 100, or 150 mg or Q28 days subcutaneous placebo or bococizumab 200 or 300 mg. Doses of bococizumab were reduced if LDL-C levels persistently decreased to ≤25 mg/dl.

The pharmacokinetics and pharmacodynamics of PF-00734200, a DPP-IV inhibitor, in healthy Japanese subjects.

Objective: To evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of PF-00734200, a potent dipeptidyl peptidase-IV (DPP-IV) inhibitor, in Japanese subjects, and compare the results with those in Western subjects.

Materials And Methods: Eight healthy Japanese subjects received a single dose of PF-00734200 10 mg, 100 mg, or placebo. Another 8 subjects received PF-00734200 20 mg or placebo single dose once daily for 6 days.

Should troponin and creatinine kinase be routinely measured after vascular surgery?

The current guidelines for the evaluation and prediction of adverse cardiovascular events (CVEs) following vascular surgery in high-risk patients recommends serial electrocardiograms (ECGs) but not biomarkers such as cTn-I and CK-MB. The objective of this study was to determine whether biomarkers should be routinely measured in high-risk patients undergoing vascular surgery. A multicenter, prospective study with investigators blinded to core laboratory results was conducted.

The Seattle Heart Failure Model: prediction of survival in heart failure.

Background: Heart failure has an annual mortality rate ranging from 5% to 75%. The purpose of the study was to develop and validate a multivariate risk model to predict 1-, 2-, and 3-year survival in heart failure patients with the use of easily obtainable characteristics relating to clinical status, therapy (pharmacological as well as devices), and laboratory parameters.

Methods And Results: The Seattle Heart Failure Model was derived in a cohort of 1125 heart failure patients with the use of a multivariate Cox model.

Efficacy of zoniporide, an Na/H exchange ion inhibitor, for reducing perioperative cardiovascular events in vascular surgery patients.

Objectives: To determine whether a novel Na+/H+ exchange ion inhibitor, zoniporide, is associated with reduced perioperative myocardial ischemic injury in high-risk surgery patients.

Design: Randomized double-blind placebo-controlled multidose trial.

Setting: Multicenter worldwide (105 centers) trial.

Importance of echocardiography in patients with severe nonischemic heart failure: the second Prospective Randomized Amlodipine Survival Evaluation (PRAISE-2) echocardiographic study.

Background: Echocardiography is used commonly in clinical practice when caring for patients with heart failure. It is unknown whether the presence of certain findings provides an incremental ability to predict survival beyond the use of baseline clinical findings alone. The second PRAISE-2 echocardiographic study was prospectively designed to identify echocardiographic predictors of survival among patients with nonischemic cardiomyopathy and heart failure and to determine if components of the echocardiographic examination add prognostic information to baseline demographic and clinical information.

Diuretic resistance predicts mortality in patients with advanced heart failure.

Background: In patients with chronic heart failure (CHF), diuretic requirements increase as the disease progresses. Because diuretic resistance can be overcome with escalating doses, the evaluation of CHF severity and prognosis may be incomplete without considering the intensity of therapy.

Methods: The prognostic importance of diuretic resistance (as evidenced by a high-dose requirement) was retrospectively evaluated in 1153 patients with advanced CHF who were enrolled in the Prospective Randomized Amlodipine Survival Evaluation (PRAISE).