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

This study has been completed.
Sponsor:
Collaborators:
Thoracic, Cardiac and Vascular Surgery, University Medicine of Goettingen
Gastroenterology and Endocrinology, University Medicine of Goettingen
Medical Statistics, University Medicine of Goettingen
Information provided by:
Herzzentrum Goettingen
ClinicalTrials.gov Identifier:
NCT00600041
First received: January 11, 2008
Last updated: March 22, 2009
Last verified: February 2008

January 11, 2008
March 22, 2009
May 2005
January 2006   (final data collection date for primary outcome measure)
Echocardiographic ejection fraction [ Time Frame: 60 min ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00600041 on ClinicalTrials.gov Archive Site
Cardiac index [ Time Frame: 60 min ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Placebo-Controlled Crossover Study for the Investigation of the Effect of Pantoprazole on Cardiac Contractility
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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Healthy
  • Drug: Pantoprazole
    80 mg IV over 2 minutes, followed by 8 mg/h IV for 60 minutes
    Other Names:
    • Pantozol i.v.
    • Protonix I.V.
  • Drug: Placebo
    Identical infusion manner like experimental arm
    Other Name: NaCl 0.9%
  • Experimental: A
    Pantoprazole IV
    Intervention: Drug: Pantoprazole
  • Placebo Comparator: B
    NaCl 0.9% IV
    Intervention: Drug: Placebo
Schillinger W, Hörnes N, Teucher N, Sossalla S, Sehrt D, Jung K, Hünlich M, Unsöld B, Geiling B, Ramadori G, Hilgers R, Schwörer 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 Mar 20; [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
November 2006
January 2006   (final data collection date for primary outcome measure)

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
Both
18 Years to 40 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00600041
HIPPO1-2004-11-01, 2004-004355-18 (EudraCT)
No
Gerd Hasenfuss/Prof. Dr., Head of dept. of Cardiology and Pneumology, Herzzentrum Goettingen, Dept. of Cardiology and Pneumology
Herzzentrum Goettingen
  • Thoracic, Cardiac and Vascular Surgery, University Medicine of Goettingen
  • Gastroenterology and Endocrinology, University Medicine of Goettingen
  • Medical Statistics, University Medicine of Goettingen
Principal Investigator: Gerd Hasenfuss, Prof. Dr. Herzzentrum Goettingen
Herzzentrum Goettingen
February 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP