The Experts below are selected from a list of 105543 Experts worldwide ranked by ideXlab platform
Roger J Hajjar - One of the best experts on this subject based on the ideXlab platform.
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calcium upregulation by percutaneous administration of gene therapy in cardiac disease cupid a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum ca2 atpase in patients with advanced heart failure
Circulation, 2011Co-Authors: Mariell Jessup, Barry H Greenberg, Donna Mancini, Thomas P Cappola, Daniel F Pauly, Brian E Jaski, Alex Yaroshinsky, Krisztina Zsebo, Howard C Dittrich, Roger J HajjarAbstract:Background—Adeno-associated virus type 1/sarcoplasmic reticulum Ca2+-ATPase was assessed in a randomized, double-blind, placebo-controlled, phase 2 study in patients with advanced heart failure. Methods and Results—Thirty-nine patients received intracoronary adeno-associated virus type 1/sarcoplasmic reticulum Ca2+-ATPase or placebo. Seven Efficacy Parameters were assessed in 4 domains: symptoms (New York Heart Association class, Minnesota Living With Heart Failure Questionnaire), functional status (6-minute walk test, peak maximum oxygen consumption), biomarker (N-terminal prohormone brain natriuretic peptide), and left ventricular function/remodeling (left ventricular ejection fraction, left ventricular end-systolic volume), plus clinical outcomes. The primary end point success criteria were prospectively defined as achieving Efficacy at 6 months in the group-level (concordant improvement in 7 Efficacy Parameters and no clinically significant worsening in any parameter), individual-level (total score fo...
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calcium upregulation by percutaneous administration of gene therapy in cardiac disease cupid a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum ca2 atpase in patients with advanced heart failure
Circulation, 2011Co-Authors: Mariell Jessup, Barry H Greenberg, Donna Mancini, Thomas P Cappola, Daniel F Pauly, Brian E Jaski, Alex Yaroshinsky, Krisztina Zsebo, Howard C Dittrich, Roger J HajjarAbstract:Background— Adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase was assessed in a randomized, double-blind, placebo-controlled, phase 2 study in patients with advanced heart failure. Methods and Results— Thirty-nine patients received intracoronary adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase or placebo. Seven Efficacy Parameters were assessed in 4 domains: symptoms (New York Heart Association class, Minnesota Living With Heart Failure Questionnaire), functional status (6-minute walk test, peak maximum oxygen consumption), biomarker (N-terminal prohormone brain natriuretic peptide), and left ventricular function/remodeling (left ventricular ejection fraction, left ventricular end-systolic volume), plus clinical outcomes. The primary end point success criteria were prospectively defined as achieving Efficacy at 6 months in the group-level (concordant improvement in 7 Efficacy Parameters and no clinically significant worsening in any parameter), individual-level (total score for predefined clinically meaningful changes in 7 Efficacy Parameters), or outcome end points (cardiovascular hospitalizations and time to terminal events). Efficacy in 1 analysis had to be associated with at least a positive trend in the other 2 analyses. This combination of requirements resulted in a probability of success by chance alone of 2.7%. The high-dose group versus placebo met the prespecified criteria for success at the group-level, individual-level, and outcome analyses (cardiovascular hospitalizations) at 6 months (confirmed at 12 months) and demonstrated improvement or stabilization in New York Heart Association class, Minnesota Living With Heart Failure Questionnaire, 6-minute walk test, peak maximum oxygen consumption, N-terminal prohormone brain natriuretic peptide levels, and left ventricular end-systolic volume. Significant increases in time to clinical events and decreased frequency of cardiovascular events were observed at 12 months (hazard ratio=0.12; P =0.003), and mean duration of cardiovascular hospitalizations over 12 months was substantially decreased (0.4 versus 4.5 days; P =0.05) on high-dose treatment versus placebo. There were no untoward safety findings. Conclusions— The Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) study demonstrated safety and suggested benefit of adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase in advanced heart failure, supporting larger confirmatory trials. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT00454818.
Herbert Lepor - One of the best experts on this subject based on the ideXlab platform.
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phase iii multicenter placebo controlled study of tamsulosin in benign prostatic hyperplasia
The Journal of Urology, 1998Co-Authors: Herbert LeporAbstract:Abstract Objectives. To evaluate the Efficacy and safety of two once-daily doses of tamsulosin, the first selective alpha 1A -antagonist studied in clinical trials. Methods. Patients with benign prostatic hyperplasia (BPH) were randomized to receive either tamsulosin (0.4 and 0.8 mg/day) or placebo (n = 756). Primary Efficacy Parameters were improvement in the total American Urological Association (AUA) symptom score and peak urinary flow (Qmax). Secondary Efficacy Parameters were improvement in measurements at individual double-blind visits corresponding to the primary Efficacy Parameters; percentage of patients with a 3-mL/s increase in Qmax; total AUA irritative, obstructive, and bother scores; individual AUA symptom scores; total, irritative, obstructive, and individual Boyarsky symptom scores; average urinary flow rate and other uroflowmetric Parameters; and investigator's global assessment. Results. Statistically significant improvements in all Efficacy Parameters were observed in tamsulosin-treated compared with placebo-treated patients. Additionally, the 0.4-mg/day dose demonstrated a rapid onset of action (4 to 8 hours) based on Qmax after the first dose of double-blind medication. A review of the safety Parameters demonstrated excellent tolerance at 1 week after the initial 0.4-mg/day dose and continued tolerance during the additional 12 weeks of 0.4- and 0.8-mg/day dosing. The incidence of positive orthostatic test results in the tamsulosin groups was comparable to that observed in the placebo group. Adverse events were comparable in the 0.4-mg/day tamsulosin and placebo groups and were somewhat higher in the 0.8-mg/day tamsulosin group. Conclusions. Tamsulosin was effective, safe, and well tolerated in the target BPH population at both the 0.4- and 0.8-mg/day dose levels, without the blood pressure-lowering effects typical of nonselective alpha-adrenergic antagonists.
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phase iii multicenter placebo controlled study of tamsulosin in benign prostatic hyperplasia tamsulosin investigator group
Urology, 1998Co-Authors: Herbert LeporAbstract:OBJECTIVES: To evaluate the Efficacy and safety of two once-daily doses of tamsulosin, the first selective alpha1A-antagonist studied in clinical trials. METHODS: Patients with benign prostatic hyperplasia (BPH) were randomized to receive either tamsulosin (0.4 and 0.8 mg/day) or placebo (n = 756). Primary Efficacy Parameters were improvement in the total American Urological Association (AUA) symptom score and peak urinary flow (Qmax). Secondary Efficacy Parameters were improvement in measurements at individual double-blind visits corresponding to the primary Efficacy Parameters; percentage of patients with a 3-mL/s increase in Qmax; total AUA irritative, obstructive, and bother scores; individual AUA symptom scores; total, irritative, obstructive, and individual Boyarsky symptom scores; average urinary flow rate and other uroflowmetric Parameters; and investigator's global assessment. RESULTS: Statistically significant improvements in all Efficacy Parameters were observed in tamsulosin-treated compared with placebo-treated patients. Additionally, the 0.4-mg/day dose demonstrated a rapid onset of action (4 to 8 hours) based on Qmax after the first dose of double-blind medication. A review of the safety Parameters demonstrated excellent tolerance at 1 week after the initial 0.4-mg/day dose and continued tolerance during the additional 12 weeks of 0.4- and 0.8-mg/day dosing. The incidence of positive orthostatic test results in the tamsulosin groups was comparable to that observed in the placebo group. Adverse events were comparable in the 0.4-mg/day tamsulosin and placebo groups and were somewhat higher in the 0.8-mg/day tamsulosin group. CONCLUSIONS: Tamsulosin was effective, safe, and well tolerated in the target BPH population at both the 0.4- and 0.8-mg/day dose levels, without the blood pressure-lowering effects typical of nonselective alpha-adrenergic antagonists.
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long term evaluation of tamsulosin in benign prostatic hyperplasia placebo controlled double blind extension of phase iii trial
Urology, 1998Co-Authors: Herbert LeporAbstract:Objectives. To evaluate the long-term Efficacy and safety of once-daily tamsulosin (0.4 and 0.8 mg), a unique selective alpha1A-adrenoceptor antagonist in patients with benign prostatic hyperplasia (BPH). Methods. This trial extended a 13-week, Phase III multicenter placebo-controlled, double-blind outpatient trial for an additional 40 weeks. Of 618 patients, 418 (68%) continued into the extension phase on the same double-blind medication and dose. The primary Efficacy Parameters were total American Urological Association (AUA) symptom score and maximum urinary flow (Qmax). Results. The mean changes in AUA symptom score from baseline to end point were statistically significant in all groups (P <0.001). Significant improvements were observed in Qmax for both tamsulosin groups but not for the placebo group. The statistically significant improvements from baseline in Efficacy Parameters observed for each tamsulosin group at the end of the 13-week Phase III trial were maintained during the long-term extension phase. Tamsulosin at both dosages was well tolerated as maintenance therapy. Clinically significant orthostatic hypotension was not observed. Vital sign changes in either hypertensive or normotensive patients were not clinically significantly different across the three groups. Conclusions. Tamsulosin once-daily at 0.4 or 0.8 mg was shown to be effective, safe, and well tolerated in the target BPH population during long-term use.
Mariell Jessup - One of the best experts on this subject based on the ideXlab platform.
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calcium upregulation by percutaneous administration of gene therapy in cardiac disease cupid a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum ca2 atpase in patients with advanced heart failure
Circulation, 2011Co-Authors: Mariell Jessup, Barry H Greenberg, Donna Mancini, Thomas P Cappola, Daniel F Pauly, Brian E Jaski, Alex Yaroshinsky, Krisztina Zsebo, Howard C Dittrich, Roger J HajjarAbstract:Background—Adeno-associated virus type 1/sarcoplasmic reticulum Ca2+-ATPase was assessed in a randomized, double-blind, placebo-controlled, phase 2 study in patients with advanced heart failure. Methods and Results—Thirty-nine patients received intracoronary adeno-associated virus type 1/sarcoplasmic reticulum Ca2+-ATPase or placebo. Seven Efficacy Parameters were assessed in 4 domains: symptoms (New York Heart Association class, Minnesota Living With Heart Failure Questionnaire), functional status (6-minute walk test, peak maximum oxygen consumption), biomarker (N-terminal prohormone brain natriuretic peptide), and left ventricular function/remodeling (left ventricular ejection fraction, left ventricular end-systolic volume), plus clinical outcomes. The primary end point success criteria were prospectively defined as achieving Efficacy at 6 months in the group-level (concordant improvement in 7 Efficacy Parameters and no clinically significant worsening in any parameter), individual-level (total score fo...
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calcium upregulation by percutaneous administration of gene therapy in cardiac disease cupid a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum ca2 atpase in patients with advanced heart failure
Circulation, 2011Co-Authors: Mariell Jessup, Barry H Greenberg, Donna Mancini, Thomas P Cappola, Daniel F Pauly, Brian E Jaski, Alex Yaroshinsky, Krisztina Zsebo, Howard C Dittrich, Roger J HajjarAbstract:Background— Adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase was assessed in a randomized, double-blind, placebo-controlled, phase 2 study in patients with advanced heart failure. Methods and Results— Thirty-nine patients received intracoronary adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase or placebo. Seven Efficacy Parameters were assessed in 4 domains: symptoms (New York Heart Association class, Minnesota Living With Heart Failure Questionnaire), functional status (6-minute walk test, peak maximum oxygen consumption), biomarker (N-terminal prohormone brain natriuretic peptide), and left ventricular function/remodeling (left ventricular ejection fraction, left ventricular end-systolic volume), plus clinical outcomes. The primary end point success criteria were prospectively defined as achieving Efficacy at 6 months in the group-level (concordant improvement in 7 Efficacy Parameters and no clinically significant worsening in any parameter), individual-level (total score for predefined clinically meaningful changes in 7 Efficacy Parameters), or outcome end points (cardiovascular hospitalizations and time to terminal events). Efficacy in 1 analysis had to be associated with at least a positive trend in the other 2 analyses. This combination of requirements resulted in a probability of success by chance alone of 2.7%. The high-dose group versus placebo met the prespecified criteria for success at the group-level, individual-level, and outcome analyses (cardiovascular hospitalizations) at 6 months (confirmed at 12 months) and demonstrated improvement or stabilization in New York Heart Association class, Minnesota Living With Heart Failure Questionnaire, 6-minute walk test, peak maximum oxygen consumption, N-terminal prohormone brain natriuretic peptide levels, and left ventricular end-systolic volume. Significant increases in time to clinical events and decreased frequency of cardiovascular events were observed at 12 months (hazard ratio=0.12; P =0.003), and mean duration of cardiovascular hospitalizations over 12 months was substantially decreased (0.4 versus 4.5 days; P =0.05) on high-dose treatment versus placebo. There were no untoward safety findings. Conclusions— The Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) study demonstrated safety and suggested benefit of adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase in advanced heart failure, supporting larger confirmatory trials. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT00454818.
Krisztina Zsebo - One of the best experts on this subject based on the ideXlab platform.
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calcium upregulation by percutaneous administration of gene therapy in cardiac disease cupid a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum ca2 atpase in patients with advanced heart failure
Circulation, 2011Co-Authors: Mariell Jessup, Barry H Greenberg, Donna Mancini, Thomas P Cappola, Daniel F Pauly, Brian E Jaski, Alex Yaroshinsky, Krisztina Zsebo, Howard C Dittrich, Roger J HajjarAbstract:Background—Adeno-associated virus type 1/sarcoplasmic reticulum Ca2+-ATPase was assessed in a randomized, double-blind, placebo-controlled, phase 2 study in patients with advanced heart failure. Methods and Results—Thirty-nine patients received intracoronary adeno-associated virus type 1/sarcoplasmic reticulum Ca2+-ATPase or placebo. Seven Efficacy Parameters were assessed in 4 domains: symptoms (New York Heart Association class, Minnesota Living With Heart Failure Questionnaire), functional status (6-minute walk test, peak maximum oxygen consumption), biomarker (N-terminal prohormone brain natriuretic peptide), and left ventricular function/remodeling (left ventricular ejection fraction, left ventricular end-systolic volume), plus clinical outcomes. The primary end point success criteria were prospectively defined as achieving Efficacy at 6 months in the group-level (concordant improvement in 7 Efficacy Parameters and no clinically significant worsening in any parameter), individual-level (total score fo...
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calcium upregulation by percutaneous administration of gene therapy in cardiac disease cupid a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum ca2 atpase in patients with advanced heart failure
Circulation, 2011Co-Authors: Mariell Jessup, Barry H Greenberg, Donna Mancini, Thomas P Cappola, Daniel F Pauly, Brian E Jaski, Alex Yaroshinsky, Krisztina Zsebo, Howard C Dittrich, Roger J HajjarAbstract:Background— Adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase was assessed in a randomized, double-blind, placebo-controlled, phase 2 study in patients with advanced heart failure. Methods and Results— Thirty-nine patients received intracoronary adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase or placebo. Seven Efficacy Parameters were assessed in 4 domains: symptoms (New York Heart Association class, Minnesota Living With Heart Failure Questionnaire), functional status (6-minute walk test, peak maximum oxygen consumption), biomarker (N-terminal prohormone brain natriuretic peptide), and left ventricular function/remodeling (left ventricular ejection fraction, left ventricular end-systolic volume), plus clinical outcomes. The primary end point success criteria were prospectively defined as achieving Efficacy at 6 months in the group-level (concordant improvement in 7 Efficacy Parameters and no clinically significant worsening in any parameter), individual-level (total score for predefined clinically meaningful changes in 7 Efficacy Parameters), or outcome end points (cardiovascular hospitalizations and time to terminal events). Efficacy in 1 analysis had to be associated with at least a positive trend in the other 2 analyses. This combination of requirements resulted in a probability of success by chance alone of 2.7%. The high-dose group versus placebo met the prespecified criteria for success at the group-level, individual-level, and outcome analyses (cardiovascular hospitalizations) at 6 months (confirmed at 12 months) and demonstrated improvement or stabilization in New York Heart Association class, Minnesota Living With Heart Failure Questionnaire, 6-minute walk test, peak maximum oxygen consumption, N-terminal prohormone brain natriuretic peptide levels, and left ventricular end-systolic volume. Significant increases in time to clinical events and decreased frequency of cardiovascular events were observed at 12 months (hazard ratio=0.12; P =0.003), and mean duration of cardiovascular hospitalizations over 12 months was substantially decreased (0.4 versus 4.5 days; P =0.05) on high-dose treatment versus placebo. There were no untoward safety findings. Conclusions— The Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) study demonstrated safety and suggested benefit of adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase in advanced heart failure, supporting larger confirmatory trials. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT00454818.
Barry H Greenberg - One of the best experts on this subject based on the ideXlab platform.
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calcium upregulation by percutaneous administration of gene therapy in cardiac disease cupid a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum ca2 atpase in patients with advanced heart failure
Circulation, 2011Co-Authors: Mariell Jessup, Barry H Greenberg, Donna Mancini, Thomas P Cappola, Daniel F Pauly, Brian E Jaski, Alex Yaroshinsky, Krisztina Zsebo, Howard C Dittrich, Roger J HajjarAbstract:Background—Adeno-associated virus type 1/sarcoplasmic reticulum Ca2+-ATPase was assessed in a randomized, double-blind, placebo-controlled, phase 2 study in patients with advanced heart failure. Methods and Results—Thirty-nine patients received intracoronary adeno-associated virus type 1/sarcoplasmic reticulum Ca2+-ATPase or placebo. Seven Efficacy Parameters were assessed in 4 domains: symptoms (New York Heart Association class, Minnesota Living With Heart Failure Questionnaire), functional status (6-minute walk test, peak maximum oxygen consumption), biomarker (N-terminal prohormone brain natriuretic peptide), and left ventricular function/remodeling (left ventricular ejection fraction, left ventricular end-systolic volume), plus clinical outcomes. The primary end point success criteria were prospectively defined as achieving Efficacy at 6 months in the group-level (concordant improvement in 7 Efficacy Parameters and no clinically significant worsening in any parameter), individual-level (total score fo...
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calcium upregulation by percutaneous administration of gene therapy in cardiac disease cupid a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum ca2 atpase in patients with advanced heart failure
Circulation, 2011Co-Authors: Mariell Jessup, Barry H Greenberg, Donna Mancini, Thomas P Cappola, Daniel F Pauly, Brian E Jaski, Alex Yaroshinsky, Krisztina Zsebo, Howard C Dittrich, Roger J HajjarAbstract:Background— Adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase was assessed in a randomized, double-blind, placebo-controlled, phase 2 study in patients with advanced heart failure. Methods and Results— Thirty-nine patients received intracoronary adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase or placebo. Seven Efficacy Parameters were assessed in 4 domains: symptoms (New York Heart Association class, Minnesota Living With Heart Failure Questionnaire), functional status (6-minute walk test, peak maximum oxygen consumption), biomarker (N-terminal prohormone brain natriuretic peptide), and left ventricular function/remodeling (left ventricular ejection fraction, left ventricular end-systolic volume), plus clinical outcomes. The primary end point success criteria were prospectively defined as achieving Efficacy at 6 months in the group-level (concordant improvement in 7 Efficacy Parameters and no clinically significant worsening in any parameter), individual-level (total score for predefined clinically meaningful changes in 7 Efficacy Parameters), or outcome end points (cardiovascular hospitalizations and time to terminal events). Efficacy in 1 analysis had to be associated with at least a positive trend in the other 2 analyses. This combination of requirements resulted in a probability of success by chance alone of 2.7%. The high-dose group versus placebo met the prespecified criteria for success at the group-level, individual-level, and outcome analyses (cardiovascular hospitalizations) at 6 months (confirmed at 12 months) and demonstrated improvement or stabilization in New York Heart Association class, Minnesota Living With Heart Failure Questionnaire, 6-minute walk test, peak maximum oxygen consumption, N-terminal prohormone brain natriuretic peptide levels, and left ventricular end-systolic volume. Significant increases in time to clinical events and decreased frequency of cardiovascular events were observed at 12 months (hazard ratio=0.12; P =0.003), and mean duration of cardiovascular hospitalizations over 12 months was substantially decreased (0.4 versus 4.5 days; P =0.05) on high-dose treatment versus placebo. There were no untoward safety findings. Conclusions— The Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) study demonstrated safety and suggested benefit of adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase in advanced heart failure, supporting larger confirmatory trials. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT00454818.
