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

NCT ID: NCT00600041

Last Updated: 2009-03-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2006-11-30

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

A

Pantoprazole IV

Group Type: EXPERIMENTAL

Pantoprazole

Intervention Type: DRUG

80 mg IV over 2 minutes, followed by 8 mg/h IV for 60 minutes

B

NaCl 0.9% IV

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Identical infusion manner like experimental arm

Interventions

Pantoprazole

80 mg IV over 2 minutes, followed by 8 mg/h IV for 60 minutes

Intervention Type: DRUG

Placebo

Identical infusion manner like experimental arm

Intervention Type: DRUG

Other Intervention Names

Pantozol i.v.; Protonix I.V.; NaCl 0.9%

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Göttingen

OTHER

Sponsor Role: collaborator

Gastroenterology and Endocrinology, University Medicine of Goettingen

OTHER

Sponsor Role: collaborator

Medical Statistics, University Medicine of Goettingen

OTHER

Sponsor Role: collaborator

Herzzentrum Goettingen

OTHER

Sponsor Role: lead

Responsible Party

Herzzentrum Goettingen, Dept. of Cardiology and Pneumology

Principal Investigators

Gerd Hasenfuss, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Herzzentrum Goettingen

Locations

Dept. of Cardiology and Pneumology; Herzzentrum Goettingen

Göttingen, , Germany

Countries

Germany

References

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.

Reference Type: RESULT

PMID: 19301059 (View on PubMed)

Other Identifiers

2004-004355-18 (EudraCT)

Identifier Type: -

Identifier Source: secondary_id

HIPPO1-2004-11-01

Identifier Type: -

Identifier Source: org_study_id