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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Heart Issues of PantoPrazOle (HIPPO)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Pantoprazole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Pantoprazole IV | Drug: Pantoprazole<br>* 80 mg IV over 2 minutes, followed by 8 mg/h IV for 60 minutes<br>* Other names: Protonix I.V.;|
| Placebo Comparator: B<br>NaCl 0.9% IV | Drug: Placebo<br>* Identical infusion manner like experimental arm<br>* Other names: NaCl 0.9%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Echocardiographic ejection fraction |  | 60 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac index |  | 60 min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Proton Pump Inhibitors, pantoprazole, Cardiac Output, Echocardiography, adverse effects