Clinical trial NCT00600041: Placebo-Controlled Crossover Study for the Investigation of the Effect of Pantoprazole on Cardiac Contractility
Official title: Heart Issues of PantoPrazOle (HIPPO)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Proton Pump Inhibitors
pantoprazole
Cardiac Output
Echocardiography
adverse effects
Lead sponsor: Herzzentrum Goettingen
Sponsor class: OTHER
Collaborators: name: University of Göttingen
name: Gastroenterology and Endocrinology, University Medicine of Goettingen
name: Medical Statistics, University Medicine of Goettingen
First posted: 2008-01-24
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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 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

Primary outcomes:
measure: Echocardiographic ejection fraction
timeFrame: 60 min
Secondary outcomes:
measure: Cardiac index
timeFrame: 60 min
Other outcomes:
Locations:
city: Goettingen
country: Germany
facility: Dept. of Cardiology and Pneumology; Herzzentrum Goettingen
Study officials:
affiliation: Herzzentrum Goettingen
name: Gerd Hasenfuss, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.