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Treatment of Coronary Heart Disease With Amiloride

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01231165
First Posted: November 1, 2010
Last Update Posted: June 11, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Clinical Research Unit at the Docent Institute of Urology
Northern Metropolitan Hospital
Venezuelan Foundation of Heart Failure
Information provided by (Responsible Party):
Antonio Delgado Leon, MD, University of Carabobo
  Purpose

Treatment of coronary artery disease is a major health care problem across the entire word, and the United States. Unfortunately, despite a number of medical advances, diagnostic procedure, or epidemiological studies, the treatment of these patients remain complex, and and at times frustrating. In fact, the COURAGE trial conducted in 50 centers across United States and Canada documented that drug treatment, coronary interventions or both were not effective solution in coronary artery diseases.

A novel approach has recently been developed, based on the critical role of the potassium (K) content in red-blood-cell in myocardial oxygenation, since oxygen and K binding by hemoglobin (red-blood-cell) occurs simultaneously in blood passing through the lungs, whereas in the organs as the heart, the hemoglobin release both Oxygen and K ions.

This apparently simple mechanisms occurs in human blood in all individuals but could be altered in subjects with acquired or hereditable defect in red-blood-cell K content. The purpose of this trial, thus, will be to evaluate the pharmacological effects of Amiloride on RBC K-uptake and transport and its impact on reversion of angina, electrocardiographic changes of myocardial ischemia and electrical regeneration of the heart in subjects with coronary artery diseases.


Condition Intervention Phase
Coronary Heart Disease Drug: Amiloride Drug: Nitrates, clopidogrel, aspirin, statins Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Comparative Randomized Single-blind Trial of Amiloride in Coronary Heart Disease

Resource links provided by NLM:


Further study details as provided by Antonio Delgado Leon, MD, University of Carabobo:

Primary Outcome Measures:
  • Regression of Angina without Recurrence [ Time Frame: Baseline, and every 6-months therafter ]
    Evaluation of Angina Class according Canadian Cardiology Society (CCS)

  • Regression of ST-T and T-waves alterations of Myocardial Ischemia [ Time Frame: Baseline and every 6-months thereafter ]
    Evaluation according Minnesota Code

  • RBC K Content [ Time Frame: Baseline and very 6-Months thereafter ]
    Obtained by a novel accurate method developed in our laboratory (Nutr Metab Cardiovasc Dis. 2002 Jun;12(3):112-116


Enrollment: 70
Study Start Date: February 2009
Study Completion Date: February 2011
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Amiloride,nitrates,clopidogrel,aspirin,statins
Comparative Efficacious Research
Drug: Amiloride
5mg/daily for 12th months
Other Names:
  • Nitrates (40mg/daily) for 12 months
  • Clopidogrel(75mg/daily)for 12 months
  • Aspirin (80mg/daily) for 12 months
  • Statins (20mg/daily) for 12 months
Active Comparator: Nitrates, clopidogrel, aspirin, statins
Comparative Efficacious Research
Drug: Nitrates, clopidogrel, aspirin, statins
Comparative Efficacious Research
Other Names:
  • Nitrates (40mg/daily) for 12 months
  • Clopidogrel(75mg/daily)for 12 months
  • Aspirin (80mg/daily) for 12 months
  • Statins (20mg/daily) for 12 months

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   35 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female; age 35-75 years having angina (Canada Cardiovascular Society Class II-IV)
  2. Essential Hypertension defined as taking at least 1 anti-hypertensive medication, or average systolic blood pressure ≥140 mm Hg, or diastolic blood pressure ≥90 mmHg
  3. ST-T changes of LVH (Romhilt-Estes or Framingham Heart Study criteria, with typical LV strain pattern, or isoelectric, inverted or biphasic T waves)
  4. ST-T changes of ischemia in resting ECG (ST depression, isoelectric, biphasic, negative or inverted T-waves)
  5. Serum potassium < 5.0 mmol/L prior to randomization
  6. Negative pregnancy test in child-bearing potential women
  7. Willing to comply with scheduled visits
  8. Informed consent form signed by the subject

Exclusion Criteria:

  1. Resistance hypertension despite 3-drugs treatment
  2. Myocardial infarction in past 90 days
  3. Coronary artery bypass graft surgery in past 90 days
  4. Atrial fibrillation with a resting heart rate > 90 bpm
  5. Percutaneous coronary intervention in past 30 days
  6. Implanted Pacemaker
  7. Stroke in past 90 days
  8. Left or Right Ventricular Branch Block
  9. Aldosterone antagonist or K sparing drug in last 7 days
  10. Intolerance to amiloride
  11. Lithium use
  12. Current participation in any other therapeutic trial
  13. Any condition that may prevent the subject from adhering to the trial protocol
  14. History of hyperkalemia (K ≥5.5 mmol/L) in the past six months or K >5.0 mmol/L within 2 weeks
  15. Chronic renal dysfunction
  16. Liver disease
  17. Chronic pulmonary disease
  18. Significant uncorrected valvular heart disease
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01231165


Locations
Venezuela
Hypertension Research Unit
Valencia, Carabobo, Venezuela, 2001
Sponsors and Collaborators
University of Carabobo
Clinical Research Unit at the Docent Institute of Urology
Northern Metropolitan Hospital
Venezuelan Foundation of Heart Failure
Investigators
Study Chair: Antonio J Delgado-Leon, MD University of Carabobo
Principal Investigator: Antonio R Delgado-Almeida, MD, FAHA, FACC, APS Clinical Research Unit at Docent Institute of Urology
Study Director: Carlos L Delgado-Leon, MD Venezuelan Foundation of Heart Failure
  More Information

Publications:
Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE 2nd, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura R, Ornato JP, Page RL, Riegel B; American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction); American College of Emergency Physicians; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; American Association of Cardiovascular and Pulmonary Rehabilitation; Society for Academic Emergency Medicine. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol. 2007 Aug 14;50(7):e1-e157. Erratum in: J Am Coll Cardiol. 2008 Mar 4;51(9):974.
Heart Disease and Stroke Statistics—2007 Update. A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee J Am Coll Cardiol, 2007; 50:1-157.
Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003 Jun 28;326(7404):1419. Erratum in: BMJ. 2006 Sep;60(9):823. BMJ. 2003 Sep 13;327(7415):586.
Nicholls SJ, Tuzcu EM, Sipahi I, Grasso AW, Schoenhagen P, Hu T, Wolski K, Crowe T, Desai MY, Hazen SL, Kapadia SR, Nissen SE. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA. 2007 Feb 7;297(5):499-508.
Simons M, Annex BH, Laham RJ, Kleiman N, Henry T, Dauerman H, Udelson JE, Gervino EV, Pike M, Whitehouse MJ, Moon T, Chronos NA. Pharmacological treatment of coronary artery disease with recombinant fibroblast growth factor-2: double-blind, randomized, controlled clinical trial. Circulation. 2002 Feb 19;105(7):788-93.
Boden WE, O'Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, Knudtson M, Dada M, Casperson P, Harris CL, Chaitman BR, Shaw L, Gosselin G, Nawaz S, Title LM, Gau G, Blaustein AS, Booth DC, Bates ER, Spertus JA, Berman DS, Mancini GB, Weintraub WS; COURAGE Trial Research Group. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007 Apr 12;356(15):1503-16. Epub 2007 Mar 26.
Jensen FB. Red blood cell pH, the Bohr effect, and other oxygenation-linked phenomena in blood O2 and CO2 transport. Acta Physiol Scand. 2004 Nov;182(3):215-27. Review.
Crawford JH, Isbell TS, Huang Z, Shiva S, Chacko BK, Schechter AN, Darley-Usmar VM, Kerby JD, Lang JD Jr, Kraus D, Ho C, Gladwin MT, Patel RP. Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation. Blood. 2006 Jan 15;107(2):566-74. Epub 2005 Sep 29.
Ellsworth ML, Forrester T, Ellis CG, Dietrich HH. The erythrocyte as a regulator of vascular tone. Am J Physiol. 1995 Dec;269(6 Pt 2):H2155-61.
Dejam A, Hunter CJ, Pelletier MM, Hsu LL, Machado RF, Shiva S, Power GG, Kelm M, Gladwin MT, Schechter AN. Erythrocytes are the major intravascular storage sites of nitrite in human blood. Blood. 2005 Jul 15;106(2):734-9. Epub 2005 Mar 17.
Bin JP, Doctor A, Lindner J, Hendersen EM, Le DE, Leong-Poi H, Fisher NG, Christiansen J, Kaul S. Effects of nitroglycerin on erythrocyte rheology and oxygen unloading: novel role of S-nitrosohemoglobin in relieving myocardial ischemia. Circulation. 2006 May 30;113(21):2502-8. Epub 2006 May 22. Erratum in: Circulation. 2006 Jul 4;114(1):e26.
Delgado-Almeida A, Delgado MC. Hereditability Defect in Red-Cell K in Hypertension. FASEB J. 2008; 22:968.8 (abstract). FASEB Experimental Biology 2008. April 5-9, San Diego, California
Fuster V. The several faces of clinical trials: from new therapies to failed preventive strategies. Nat Clin Pract Cardiovasc Med. 2006 Apr;3(4):173.
Delgado-Almeida A, Delgado-Leon C, Delgado-Leon AJ. Amiloride and red blood cell potassium transport in coronary artery disease: Reversion of the clinical and ECG alterations (abstract). 2007 Scientific Meeting of the Inter-American Society of Hypertension and the Consortium for Southeastern Hypertension Control. Miami 6-10, 2007.
Finimundi HC, Caramori PA, Parker JD. Effect of diuretic therapy on exercise capacity in patients with chronic angina and preserved left ventricular function. J Cardiovasc Pharmacol. 2007 May;49(5):275-9.

Responsible Party: Antonio Delgado Leon, MD, Prof. of Medicine, MD, University of Carabobo
ClinicalTrials.gov Identifier: NCT01231165     History of Changes
Other Study ID Numbers: UIC-5 2008
First Submitted: October 29, 2010
First Posted: November 1, 2010
Last Update Posted: June 11, 2012
Last Verified: April 2012

Additional relevant MeSH terms:
Heart Diseases
Coronary Disease
Coronary Artery Disease
Myocardial Ischemia
Cardiovascular Diseases
Vascular Diseases
Arterial Occlusive Diseases
Arteriosclerosis
Aspirin
Ticlopidine
Clopidogrel
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Amiloride
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists


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