Placebo-Controlled Crossover Study for the Investigation of the Effect of Pantoprazole on Cardiac Contractility (HIPPO)

Heart Issues of PantoPrazOle (HIPPO)

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Pantoprazole; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: NaCl 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Echocardiographic ejection fraction	60 min

Secondary Outcome Measures

Outcome Measure	Time Frame
Cardiac index	60 min

Collaborators and Investigators

• Sponsor: Herzzentrum Goettingen
• Collaborators: University of Göttingen; Medical Statistics, University Medicine of Goettingen; Gastroenterology and Endocrinology, University Medicine of Goettingen
• Investigators: Principal Investigator: Gerd Hasenfuss, Prof. Dr., Herzzentrum Goettingen

Publications and helpful links

General Publications

• Schillinger W, Hornes N, Teucher N, Sossalla S, Sehrt D, Jung K, Hunlich M, Unsold B, Geiling B, Ramadori G, Hilgers R, Schworer 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 Jun;98(6):391-9. doi: 10.1007/s00392-009-0012-6. Epub 2009 Mar 20.

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): January 1, 2006
• Study Completion (Actual): November 1, 2006

Study Registration Dates

• First Submitted: January 11, 2008
• First Submitted That Met QC Criteria: January 23, 2008
• First Posted (Estimate): January 24, 2008

Study Record Updates

• Last Update Posted (Estimate): March 24, 2009
• Last Update Submitted That Met QC Criteria: March 22, 2009
• Last Verified: February 1, 2008

More Information

Terms related to this study

• Keywords: Echocardiography; adverse effects; Cardiac Output; Proton Pump Inhibitors; pantoprazole
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Pantoprazole
• Other Study ID Numbers: HIPPO1-2004-11-01; 2004-004355-18 (EudraCT)