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

Official Title: “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.

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.

Intervention(s) in this Clinical Trial

• Drug: Pantoprazole
  • 80 mg IV over 2 minutes, followed by 8 mg/h IV for 60 minutes
• Drug: Placebo
  • Identical infusion manner like experimental arm

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Pantoprazole IV
• Placebo Comparator: B
  • NaCl 0.9% IV

Primary Measures

• Echocardiographic ejection fraction
  • Time Frame: 60 min
    Safety Issue?: Yes

Secondary Measures

• Cardiac index
  • Time Frame: 60 min
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 40 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: Herzzentrum Goettingen Other

Overall Clinical Trial Officials and Contacts

Gerd Hasenfuss, Prof. Dr. Principal Investigator Herzzentrum Goettingen  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00600041

Study ID Number: HIPPO1-2004-11-01

ClinicalTrials.gov Identifier: NCT00600041

Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Herzzentrum Goettingen - Heart Center of Goettingen