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

Herzzentrum Goettingen

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Placebo; Drug: Pantoprazole

Study type: Interventional

Funder types: Other

Identifiers

NCT00600041

HIPPO1-2004-11-01

2004-004355-18 (EudraCT)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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20 participants in 2 patient groups, including a placebo group

A

Experimental group

Description:

Pantoprazole IV

Treatment:

Drug: Pantoprazole

B

Placebo Comparator group

Description:

NaCl 0.9% IV

Treatment:

Drug: Placebo