Placebo-Controlled Crossover Study for the Investigation of the Effect of Pantoprazole on Cardiac Contractility - Full Text View

Sponsor:	Herzzentrum Goettingen
Collaborators:	Thoracic, Cardiac and Vascular Surgery, University Medicine of Goettingen Gastroenterology and Endocrinology, University Medicine of Goettingen Medical Statistics, University Medicine of Goettingen
Information provided by:	Herzzentrum Goettingen
ClinicalTrials.gov Identifier:	NCT00600041

Purpose

Recently, negative inotropy of pantoprazole has been shown in isolated human myocardium. This study was designed to test the clinical relevance of this finding in healthy volunteers by measuring left ventricular function during infusion of a common intravenous high dose regimen of pantoprazole.

Condition	Intervention	Phase
Healthy	Drug: Pantoprazole Drug: Placebo	Phase I

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Basic Science
Official Title:	Heart Issues of PantoPrazOle (HIPPO)

Resource links provided by NLM:

Drug Information available for: Pantoprazole Pantoprazole Sodium

U.S. FDA Resources

Further study details as provided by Herzzentrum Goettingen:

Primary Outcome Measures:

Echocardiographic ejection fraction [ Time Frame: 60 min ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Cardiac index [ Time Frame: 60 min ] [ Designated as safety issue: Yes ]

Enrollment:	20
Study Start Date:	May 2005
Study Completion Date:	November 2006
Primary Completion Date:	January 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A Pantoprazole IV	Drug: Pantoprazole 80 mg IV over 2 minutes, followed by 8 mg/h IV for 60 minutes Other Names: Pantozol i.v. Protonix I.V.
Placebo Comparator: B NaCl 0.9% IV	Drug: Placebo Identical infusion manner like experimental arm Other Name: NaCl 0.9%

Detailed Description:

Purpose: Reports on cardiac problems with oral proton pump inhibitors have caused extensive safety reviews by the U.S. Food and Drug Administration. We provide additional data on acute cardiac effects of an intravenous application.

Methods: Echocardiography was performed in 18 healthy volunteers after administration of a common high dose regimen of pantoprazole (80 mg IV bolus followed by 8 mg/h for 1h) or placebo. Design: Randomized, double-blind, placebo-controlled crossover trial.

Results: EF [%, means+/-S.E.] in the treatment group (placebo group) was 60.7+/-1.1 (61.2+/-1.7) at baseline, and 62.6+/-1.1 (62.1+/-1.9), 64.7+/-1.6 (63.5+/-1.3), 62.6+/-1.6 (61.0+/-1.6) and 63.0+/-1.4 (61.8+/-1.5) at 7.5, 15, 30 and 60 min after bolus application, respectively (p = n.s.). Similarly, no significant changes were found for cardiac output, cardiac index, blood pressure, and heart rate. In contrast, gastric pH that was used as a treatment control was significantly increased 60 min after application of pantoprazole as compared to baseline and to placebo.

Conclusions: Pantoprazole for injection is safe in healthy subjects with respect to cardiac contractile function. However, in view of recent reports of negative inotropy of the drug further studies in heart failure patients are required.

Eligibility

Ages Eligible for Study:	18 Years to 40 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Age > 18 or < 40 years
No signs of overt heart failure
Echocardiographic ejection fraction >= 55%
Body Mass Index 20 - 25 kg/m²
Excellent sonographic conditions
Non-smoker
Informed consent

Exclusion Criteria:

History of cardiac disease
History of other relevant pre-existing illness
Pathologic findings in clinical examinations
Pathologic echocardiographic findings
Pathologic ECG findings
Pathologic laboratory findings
Pregnancy and lactation
No or insufficient contraception
Intolerance of pantoprazole
Alcohol or drug abuse

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00600041

Locations

Germany
Dept. of Cardiology and Pneumology; Herzzentrum Goettingen
Goettingen, Germany, 37099

Sponsors and Collaborators

Herzzentrum Goettingen

Thoracic, Cardiac and Vascular Surgery, University Medicine of Goettingen

Gastroenterology and Endocrinology, University Medicine of Goettingen

Medical Statistics, University Medicine of Goettingen

Investigators

Principal Investigator:

Gerd Hasenfuss, Prof. Dr.

Herzzentrum Goettingen

More Information

Additional Information:

Herzzentrum Goettingen - Heart Center of Goettingen This link exits the ClinicalTrials.gov site

Publications:

Schillinger W, Hörnes N, Teucher N, Sossalla S, Sehrt D, Jung K, Hünlich M, Unsöld B, Geiling B, Ramadori G, Hilgers R, Schwörer H, Hasenfuss G. Recent in vitro findings of negative inotropy of pantoprazole did not translate into clinically relevant effects on left ventricular function in healthy volunteers. Clin Res Cardiol. 2009 Mar 20; [Epub ahead of print]

Responsible Party:	Gerd Hasenfuss/Prof. Dr., Head of dept. of Cardiology and Pneumology, Herzzentrum Goettingen, Dept. of Cardiology and Pneumology
ClinicalTrials.gov Identifier:	NCT00600041 History of Changes
Other Study ID Numbers:	HIPPO1-2004-11-01, 2004-004355-18 (EudraCT)
Study First Received:	January 11, 2008
Last Updated:	March 22, 2009
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Herzzentrum Goettingen:

Proton Pump Inhibitors
pantoprazole
Cardiac Output
Echocardiography
adverse effects

Additional relevant MeSH terms:

Pantoprazole
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

Pharmacologic Actions
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012