Influence of Pantoprazole on Human Myocardial Contractility at Patients With Congestive Heart Failure

Recently literature revealed facts, that show H+/K+ ATPase expression is not limited tot he stomach. H+/K+ ATPase was also found in smooth muscle cells and in other tissues (McCabe, R.D. et al., Am J Physiol. 1992). For myocard a localisation is only proven for rats yet (Beisvag, V. et al., Acta Physiol Scand. 2003). Moreover biochemical hints lead us to a highly probability of a myocardial H+/K+ ATPase (Nagashima, R. et al., Jpn Heart J. 1999).

Study Overview

• Status: Withdrawn
• Conditions: Congestive Heart Failure
• Intervention / Treatment: Drug: Pantoprazole; Drug: Pantoprazole

Detailed Description

Recently literature revealed facts, that show H+/K+ ATPase expression is not limited tot he stomach. H+/K+ ATPase was also found in smooth muscle cells and in other tissues (McCabe, R.D. et al., Am J Physiol. 1992). For myocard a localisation is only proven for rats yet (Beisvag, V. et al., Acta Physiol Scand. 2003). Moreover biochemical hints lead us to a highly probability of a myocardial H+/K+ ATPase (Nagashima, R. et al., Jpn Heart J. 1999). Aim of our clinical study is to examine, whether proton pump inhibitors have an influence on myocardial contraction of human myocard and we want to ascertain the amount of influence of a H+/K+ ATPase on myocardial contraction. Therefore the mechanism of a putative inhibition by proton pump inhibitors is at our focus. These findings will be of major credit regarding treatment of patients with congestive heart failure with common proton pump inhibitors. We want to find out, whether this intake may have a negative inotropic effect on the heart failure myocard.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Frankfurt am Main, Germany, 60590
    • Johann Wolfgang Goethe University Hospitals, Department of Cardiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Only patients older than 18 years. Range 18 to 80 years
2. Only cooperative patients
3. Only patients with a need for a coronary angiography, independently from our study
4. Only patients with a left ventricular ejection fraction as demanded in the study protocol
5. Only patients with clinical symptoms of congestive heart failure, corresponding to New York Heart Association stage NYHA II or III
6. Only patients without oral or i.v. application of a proton pump inhibitor up to 48 hours prior to the study catheterization

Exclusion Criteria:

1. Manifest or severe accompanying diseases, despite of diabetes mellitus
2. Intravascular or oral application of proton pump inhibitors within the last 48 hours
3. Intake of Metformin within the last 24 hours
4. Status post heart transplant
5. Pregnancy
6. Known intolerance of pantoprazole
7. severe side effects of the tested substance pantoprazole, as well as pharmacokinetic interactions through CYP isoenzymes
8. Existance of side effects as given in the pantoprazole drug information, among others disturbances of blood- and lymphatic system, leukopenia, thrombopenia, affections of gastrointestinal tract, nerve system affections, psychiatric affections, renal or bladder affections
9. Participation in a other clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Measurement before Pantoprazole application	Drug: Pantoprazole; Pantoprazole 160 mg I.V.; Other Names: Protonix; Drug: Pantoprazole; Pantoprazole 160 mg intravenously (IV); Other Names: Protonix
Experimental: 2; Measurements after Pantoprazole application	Drug: Pantoprazole; Pantoprazole 160 mg I.V.; Other Names: Protonix; Drug: Pantoprazole; Pantoprazole 160 mg intravenously (IV); Other Names: Protonix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Aim of our clinical study is to examine, whether proton pump inhibitors have an influence on myocardial contraction of human myocard and we want to ascertain the amount of influence of a H+/K+ ATPase on myocardial contraction.	6 months

Collaborators and Investigators

• Sponsor: Johann Wolfgang Goethe University Hospital
• Investigators: Principal Investigator: Volker Schächinger, MD, Johann Wolfgang Goethe University Hospital

Publications and helpful links

General Publications

• Schillinger W, Teucher N, Sossalla S, Kettlewell S, Werner C, Raddatz D, Elgner A, Tenderich G, Pieske B, Ramadori G, Schondube FA, Kogler H, Kockskamper J, Maier LS, Schworer H, Smith GL, Hasenfuss G. Negative inotropy of the gastric proton pump inhibitor pantoprazole in myocardium from humans and rabbits: evaluation of mechanisms. Circulation. 2007 Jul 3;116(1):57-66. doi: 10.1161/CIRCULATIONAHA.106.666008. Epub 2007 Jun 18.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: June 13, 2008
• First Submitted That Met QC Criteria: June 17, 2008
• First Posted (Estimate): June 18, 2008

Study Record Updates

• Last Update Posted (Estimate): February 11, 2014
• Last Update Submitted That Met QC Criteria: February 10, 2014
• Last Verified: June 1, 2008

More Information

Terms related to this study

• Keywords: Pantoprazole; congestive heart failure
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Pantoprazole
• Other Study ID Numbers: panto001