In the presence of a significant coronary artery stenosis and randomization to the intervention group: Catheter-based permanent occlusion of the ipsilateral (to the culprit coronary lesion) IMA will be performed at the projected height of inferior vena cava confluence and right atrium using a dedicated occlusion device (Amplatzer vascular plug 4, CE0086).

In the presence of a significant coronary artery stenosis, and randomization to the sham-procedure: IMA will be selectively intubated using an appropriate catheter. Angiography of the IMA and the pericardiacophrenic branch will be performed.

Coronary Artery Disease

Internal Mammary-Coronary Artery Anastomosis

Ischemia

Circulation, Collateral

Amplatzer vascular plug 4

Sham Control

University Hospital Inselspital, Bern

Clinical Efficacy of Permanent Internal Mammary Artery Occlusion in Stable Coronary Artery Disease

Treadmill exercise time at follow-up minus treadmill exercise time at baseline exam (difference measured in seconds)

Occurence of Angina pectoris during a controlled 1-minute ostial coronary occlusion for collateral flow index measurement. The occurence will be presented in percent (number of patient with Angina pectoris during occlusion / total number of patients * 100 ) per group (intervention and sham control). If no adequate collateral flow exists, all patient (=100%) should develop angina pectoris during a one-minute occlusion

Change in coronary CFI (unitless) at follow-up (week 6) vs baseline. Collateral flow index (CFI), the ratio of mean occlusive divided by mean non-occlusive blood pressure, both subtracted by central venous pressure. Range: 0-1. With a CFI of 0.215, a sufficient collateral blood flow exists and can prevent myocardial infarction.

During a controlled 1-minute ostial coronary occlusion for collateral flow index measurement (in mV)

Change in coronary FFR (unitless) at follow-up (week 6) vs baseline.

Change in SAQ at follow-up (week 6) vs baseline. The SAQ quantifies 3 domains measuring the impact of angina on patients' health status. Scores are generated for each domain and are scaled 0-100, with 0 denoting the worst and 100 the best possible status. The total score is derived as the average of the three domain scores (again: with 0 denoting the worst and 100 the best possible status)

Change in time (in seconds) to 0.1mV ECG ST-segment depression at follow-up(week6) vs baseline

University Hospital Inselspital, Berne

The patients undergoing elective and complete CABG revascularization performed by the same surgeon, will be randomized in two different groups to receive, in the three days before surgery, Ranolazine at a dose of 375 mg twice daily.

The patients undergoing elective and complete CABG revascularization performed by the same surgeon, will be randomized in two different groups to receive, in the three days before surgery, placebo twice daily.

Myocardial Stunning

Patients in this arm receive Ranolazine at a dose of 375 mg twice daily in the three days before surgery

Ranolazine

Patients receive Placebo twice daily in the three days before surgery

Placebo

Ranolazine a Potential New Therapeutic Application

Ranolazine Myocardial Protection in Complete Coronary Artery Bypass Grafting: A Randomized-controlled Trial

A blood sample will be collected by coronary sinus and the sample sent by our laboratories to assess the concentration in µg/l of cardiac troponins directly in venous blood before cardiopulmonary by-pass and after the release of aortic cross clamp, about 10 minutes after the end of reperfusion.

Earlobe arterialized blood sample will be collected by radial artery coronary sinus and the sample sent by our laboratories to assess the concentration of VO2 and O2ER in ml/min in venous blood before cardiopulmonary by-pass and after the release of aortic cross clamp, about 10 minutes after the end of reperfusion.

Earlobe arterialized blood sample will be collected by radial artery and coronary sinus and the sample sent by our laboratories to assess the concentration of lactates in mmol/L in venous blood before cardiopulmonary by-pass and after the release of aortic cross clamp, about 10 minutes after the end of reperfusion.

A blood sample will be collected by peripheral vein and the sample sent by our laboratories to assess the concentration in µg/l of cardiac troponins Since arrival on intensive care unit and 6, 12, 24, 48 h after unclamping of the aorta.

Transesophageal echocardiographic study will be performed by two expert echocardiographers following the protocols of the Society of Cardiovascular Anesthesiologists and American Society of Echocardiography. Left ventricle myocardial performance index, LVEF (%), left ventricular regional wall motion, E/A ratio, E', E/E' and deceleration time (DT) of mitral inflow velocity will be measured; these measurements will be obteined.

Hemodynamic measurements will be obtained by an arterial and a pulmonary artery catheter (PAC) inserted before surgery, and will include arterial pressure (systolic, diastolic and mean pressure), pulmonary artery pressure (PAP), right atrial pressure (RAP), pulmonary artery wedge pressure (PAWP), cardiac output (CO) and cardiac index (CI), systemic vascular resistance (SVR), left ventricular stroke work (LVSW), left stroke volume variaton (LSVV) and coronary artery perfusion pressure (CPP).

New-onset atrial fibrillation, ventricular arrhythmia, low cardiac output syndrome (LCOS), inotropic support and/or intraaortic balloon pump >24 hours, myocardial infarction) and intensive care unit and hospital length of stay between two groups.

Temistocle Taccheri

MD, Resident in Anesthesia and Intensive Care Department

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

In the open-label treatment phase (approximately 4 weeks' duration), patients were given open-label ranolazine extended-release (ER) tablets 500 mg twice daily and continued to take their baseline antianginal medications. Patients completed self-administered questionnaires to document angina symptoms, response to antianginal treatment, and functional status. They also completed daily diaries to document the occurrence of angina episodes and NTG consumption.

Sex: Female, Male

Race/Ethnicity, Customized

Region of Enrollment

Body Mass Index

Weight

Changes from BL in angina frequency items following ranolazine treatment were measured. Analysis: multiple linear regression; response variable: ΔWISQ - ΔSAQ; independent variables: age and BL WISQ and SAQ scores. WISQ items: 15 points (higher=more severe state); SAQ items: 12 points (lower=more severe state). WISQ scores were recalibrated by multiplying by .75. Noninferiority was to be considered demonstrated if the lower limit of a 2-sided 95% CI for WISQ mean - SAQ mean was above the prespecified margin (WISQ vs SAQ difference of -2).

Determine Whether the WISQ is Noninferior to the Seattle Angina Questionnaire (SAQ) With Regard to Angina Frequency Items Based on Changes From Baseline (BL) in the Angina Frequency Items of the WISQ With the SAQ Following Ranolazine Treatment

Changes from BL in stress, excitement, temperature, satiety, anger, and other limitation items following ranolazine treatment were measured. Analysis: multiple linear regression; response variable: ΔWISQ - ΔSAQ; independent variables: age and BL WISQ and SAQ scores. WISQ items: 27 points (higher=more severe state); SAQ items: 45 points (lower=more severe state). WISQ scores were recalibrated by multiplying by 15/27. Noninferiority was to be considered demonstrated if the lower limit of a 2-sided 95% CI for WISQ mean - SAQ mean was above the prespecified margin (WISQ vs SAQ difference of -2).

Compare Changes From Baseline (BL) in the Physical Limitation Items of the WISQ With the SAQ Following Ranolazine Treatment

Compare Changes From Baseline (BL) in Other Like Items of the WISQ With the SAQ Following Ranolazine Treatment

Validity of the WISQ was assessed by regression analysis. Results of this analysis are reported as the estimated coefficient of determination (R^2) of the WISQ Total Score at 4 weeks regressed on 4-week angina frequency, 4-week NTG use, and DASI score at 4 weeks. For mean (SEM) Baseline and Week 4 values for angina frequency and NTG use, please refer to Secondary Outcome Measures 7 and 8. For mean (SEM) Baseline and Week 4 DASI values, please refer to Secondary Outcome Measure 9.

Evaluate the Validity of the WISQ in Women With Chronic Angina Based on Changes in Patient-reported Angina Frequency and Nitroglycerin (NTG) Consumption Before and Following Treatment With Ranolazine Assessed as Coefficient of Determination (R^2)

Angina episodes were recorded by subjects in their diaries. Weekly frequency of angina episodes was calculated for the two-week baseline period and the last two weeks of the study.

Determine the Effect of Ranolazine on Angina Frequency as Measured by Patient-reported Diaries

Nitroglycerin use was recorded by subjects in their diaries. Weekly frequency of NTG use was calculated for the two-week baseline period and the last two weeks of the study.

Determine the Effect of Ranolazine on Nitroglycerin Consumption as Measured by Patient-reported Diaries

The DASI was analyzed as mean values at baseline and Week 4. The DASI is a self-administered questionnaire that measures a patient's functional capacity. It can be used to get a rough estimate of a patient's peak oxygen uptake. The maximum score for the DASI is 58.2 (better functional ability/capacity) and the minimum score is 0 (worse functional ability/capacity).

Determine Changes From Baseline in the Duke Activity Status Index (DASI) Following Ranolazine Treatment

Reliability of the WISQ was assessed by estimating Cronbach's alpha (standardized); values of 0.7 or higher were to be considered adequate. (Standardized Cronbach's alpha is a coefficient of reliability or consistency, and is a function of the average inter-item correlation.) Cronbach's alpha was calculated for the WISQ instrument overall and for the Angina Frequency/Severity and Angina Stability subscales. Missing item responses were not imputed.

Evaluate the Reliability of the WISQ in Women With Chronic Angina Based on Changes in Patient-reported Angina Frequency and NTG Consumption Before and Following Treatment With Ranolazine Assessed as Cronbach's Alpha Value

Responsiveness of the WISQ was assessed as the estimated coefficient of determination (R^2) of the change from baseline WISQ Total Score at 4 weeks regressed on change from baseline angina frequency and change from baseline NTG use. For mean (SEM) Baseline and Week 4 values for angina frequency and NTG use, please refer to Secondary Outcome Measures 7 and 8.

Evaluate the Responsiveness of the WISQ in Women With Chronic Angina Based on Changes in Patient-reported Angina Frequency and NTG Consumption Before and Following Treatment With Ranolazine Assessed by Regression Analysis

The DASI is a self-administered questionnaire that measures a patient's functional capacity. It can be used to get a rough estimate of a patient's peak oxygen uptake. The maximum score for the DASI is 58.2 (better functional ability/capacity) and the minimum score is 0 (worse functional ability/capacity). The planned analysis was the amount of variation in WISQ and SAQ score changes from baseline explained by changes in angina frequency, NTG use, and DASI score assessed by multiple linear regression analysis.

Evaluate the Degree of Correlation Between Changes From Baseline in Items of the WISQ and SAQ With Changes From Baseline in Angina Frequency and NTG Diary Data and the DASI

Overall Study

Emmanuelle Bellemin, Senior Manager, Regulatory Affairs

Chronic Angina

The University of Alabama at Birmingham

Cardiovascular Consultants, Ltd.

Cardiology Consultants of Orange County

Access Clinical Trials/Cardiovascular Research Institute (ACT/CVRI)

Escondido Cardiology Associates

Cedars-Sinai Medical Center

Mission Internal Medical Group

South Denver Cardiology Associates, PC

Guerra Cardiology

Jacksonville Center for Clinical Research

St. Luke Cardiology Associates

Jacksonville Heart Center, PA

Emory University & Grady Health System

Mercy Physician Group Cardiology

North Shore Cardiology

Gateway Cardiology, P.C.

Northern Indiana Research Alliance

Ashland Hospital Corporation d/b/a King's Daughters Medical Center

University of Louisville, Division of Cardiovascular Medicine

Integrated Cardiology Consultants, LLC d.b.a. Bryan LGH Heart Institute

Albany Associates in Cardiology

Total Heart Care, PC

The Lindner Clinical Trial Center

St. Vincent Mercy Medical Center, Cardiac Research

BlueStem Cardiology

Tri-State Medical Group, Cardiology, Sewickley Valley Medical Group, Cardiology

Cardiology Consultants of Philadelphia

An Open-label, Multi-center Study Evaluating the Validity, Reliability, and Responsiveness of a New Female-specific Angina Questionnaire in Women With Chronic Angina Treated With Ranolazine Extended-release Tablets (CVT 3041)

An Open-label, Multi-center Study Evaluating the Validity, Reliability, and Responsiveness of a New Women's Ischemia Symptom Questionnaire in Women With Chronic Angina Treated With Ranolazine Extended-release Tablets (CVT 3041)

Gilead Sciences

Topotecan 3.5 mg/m^2 + Sorafenib dose escalation:

Topotecan 3.5 mg/m^2 + Sorafenib 400 mg po daily.

Topotecan 3.5 mg/m^2 + Sorafenib assigned dose level:
Sorafenib Dose level -1=200 mg po daily Sorafenib Dose level 1=400 mg po daily Sorafenib Dose level 2=400 mag po bid

Phase I

Phase II

Total

Race (NIH/OMB)

ECOG: Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) from 0-5 that describes a patient's level of functioning where 0=Fully active, able to carry on all pre-disease performance without restriction and 5=Dead

Eastern Cooperative Onocology Group (ECOG) Perfomance Status

Origin of Cancer

Histology

Number of Prior Therapies

Response Evaluation Criteria in Solid Tumors (RECIST):
Measurable disease is defined by the presence of at least one measureable lesion. If the measureable disease is restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology.
Detectable disease is defined as a patient who does not have measureable disease, but has at least one: 1)CA-125 >= 2x ULN w/in 14d prior to registration 2)Ascites and/or pleural effusion attributed to tumor; 3)solid and/or cystic abnormalities on radiographic imaging that don't meet RECIST definitions for target lesions.

Response Evaluation

Platinum Sensitivity

CA125 at Enrollment

An initial 3 patients will be enrolled at dose level 1. If all 3 patients in dose level 1 complete the first cycle of therapy without a dose limiting toxicity (DLT), 3 patients will be enrolled at dose level 2. If 0 of 3 or 1 of 6 patients in dose level 2 experience a DLT, all subsequent patients will be enrolled in the Phase II cohort at dose level 2. If 2 of the first 3 or 2 of the total 6 patients experience DLT at dose level 2, then dose level 1 will be considered the MTD and used in the second phase.

Phase I Participants

Maximum Tolerated Dose (MTD)

To assess response in patients with recurrent or resistant epithelial ovarian cancer treated with Sorafenib plus Topotecan. Reponse evaluated per RECIST criteria where:
Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started

Percentage of Participants With Response

To determine the progression-free survival of patients treated with Sorafenib plus Topotecan.

Topotecan 3.5 mg/m^2 + Sorafenib 400 mg po daily during phase II.
During phase I:
Topotecan 3.5 mg/m^2 + Sorafenib assigned dose level:
Sorafenib Dose level -1=200 mg po daily Sorafenib Dose level 1=400 mg po daily Sorafenib Dose level 2=400 mag po bid

Phase I & II

Progression-free Survival

To determine the rate of clinical benefit defined as the percentage of patients experiencing an objective response or a CA125 response.

Clinical Benefit

To determine duration of stable disease, in months

Duration of Stable Disease

Principal Investigator

Phase I/Phase II

Ovarian Cancer

Phase I: Dose Escalation, Phase II: MTD
Dose level -1: 200mg po daily Dose level 1: 400mg po daily (MTD) Dose level 2: 400mg po bid

Sorafenib

3.5mg/m2 weekly, 3 weeks on and one week off.

Topotecan

Medical & Surgical Specialists, LLC

Oncology Hematology Associates of SW Indiana

Fort Wayne Oncology & Hematology, Inc

Indiana University Simon Cancer Center

St. Vincent Hospital Cynecologic Oncology

Arnett Cancer Care

Medical Consultants, P.C.

Schwartz Gynecologic Oncology, PLLC

Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer

A Phase I/II Study of Sorafenib in Combination With Topotecan for the Treatment of Platinum-Resistant Recurrent Ovarian Cancer or Primary Peritoneal Carcinomatosis: Hoosier Oncology Group GYN06-111

antianginal/stroke

Clinical Efficacy of Permanent Internal Mammary Artery Occlusion in Stable Coronary Artery Disease

Ranolazine a Potential New Therapeutic Application

An Open-label, Multi-center Study Evaluating the Validity, Reliability, and Responsiveness of a New Female-specific Angina Questionnaire in Women With Chronic Angina Treated With Ranolazine Extended-release Tablets (CVT 3041)

Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer

Den mest kompletta databasen med medicinska örter som stöds av vetenskapen