Treatment of Coronary Heart Disease With Amiloride

NCT01231165 | Completed Phase 2

• 1 other identifier: UIC-5 2008
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Coronary Heart Disease

Outcome Measures

Primary Outcomes (3)

• Regression of Angina without Recurrence

  Evaluation of Angina Class according Canadian Cardiology Society (CCS)

  Baseline, and every 6-months therafter

• Regression of ST-T and T-waves alterations of Myocardial Ischemia

  Evaluation according Minnesota Code

  Baseline and every 6-months thereafter

• RBC K Content

  Obtained by a novel accurate method developed in our laboratory (Nutr Metab Cardiovasc Dis. 2002 Jun;12(3):112-116

  Baseline and very 6-Months thereafter

Study Arms (2)

Amiloride,nitrates,clopidogrel,aspirin,statins

EXPERIMENTAL

Comparative Efficacious Research

Drug: Amiloride

Nitrates, clopidogrel, aspirin, statins

ACTIVE COMPARATOR

Comparative Efficacious Research

Drug: Nitrates, clopidogrel, aspirin, statins

Interventions

Amiloride DRUG

5mg/daily for 12th months

Also known as: Nitrates (40mg/daily) for 12 months, Clopidogrel(75mg/daily)for 12 months, Aspirin (80mg/daily) for 12 months, Statins (20mg/daily) for 12 months

Amiloride,nitrates,clopidogrel,aspirin,statins

Nitrates, clopidogrel, aspirin, statins DRUG

Comparative Efficacious Research

Also known as: Nitrates (40mg/daily) for 12 months, Clopidogrel(75mg/daily)for 12 months, Aspirin (80mg/daily) for 12 months, Statins (20mg/daily) for 12 months

Nitrates, clopidogrel, aspirin, statins

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female; age 35-75 years having angina (Canada Cardiovascular Society Class II-IV)
• 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
• ST-T changes of LVH (Romhilt-Estes or Framingham Heart Study criteria, with typical LV strain pattern, or isoelectric, inverted or biphasic T waves)
• ST-T changes of ischemia in resting ECG (ST depression, isoelectric, biphasic, negative or inverted T-waves)
• Serum potassium \< 5.0 mmol/L prior to randomization
• Negative pregnancy test in child-bearing potential women
• Willing to comply with scheduled visits
• Informed consent form signed by the subject

You may not qualify if:

• Resistance hypertension despite 3-drugs treatment
• Myocardial infarction in past 90 days
• Coronary artery bypass graft surgery in past 90 days
• Atrial fibrillation with a resting heart rate \> 90 bpm
• Percutaneous coronary intervention in past 30 days
• Implanted Pacemaker
• Stroke in past 90 days
• Left or Right Ventricular Branch Block
• Aldosterone antagonist or K sparing drug in last 7 days
• Intolerance to amiloride
• Lithium use
• Current participation in any other therapeutic trial
• Any condition that may prevent the subject from adhering to the trial protocol
• History of hyperkalemia (K ≥5.5 mmol/L) in the past six months or K \>5.0 mmol/L within 2 weeks
• Chronic renal dysfunction

Sponsors & Collaborators

• University of Carabobo: lead
• Clinical Research Unit at the Docent Institute of Urology: collaborator
• Northern Metropolitan Hospital: collaborator
• Venezuelan Foundation of Heart Failure: collaborator

Study Sites (1)

Hypertension Research Unit

Valencia, Carabobo, 2001, Venezuela

Location

Related Publications (15)

• ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction. J Am Coll Cardiol, 2007; 50:1-157

  BACKGROUND

• Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007 Feb 6;115(5):e69-171. doi: 10.1161/CIRCULATIONAHA.106.179918. Epub 2006 Dec 28. No abstract available.

  PMID: 17194875 BACKGROUND

• Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003 Jun 28;326(7404):1419. doi: 10.1136/bmj.326.7404.1419.

  PMID: 12829553 BACKGROUND

• 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. doi: 10.1001/jama.297.5.499.

  PMID: 17284700 BACKGROUND

• 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. doi: 10.1161/hc0802.104407.

  PMID: 11854116 BACKGROUND

• 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. doi: 10.1056/NEJMoa070829. Epub 2007 Mar 26.

  PMID: 17387127 BACKGROUND

• 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. doi: 10.1111/j.1365-201X.2004.01361.x.

  PMID: 15491402 BACKGROUND

• 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. doi: 10.1182/blood-2005-07-2668. Epub 2005 Sep 29.

  PMID: 16195332 BACKGROUND

• 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. doi: 10.1152/ajpheart.1995.269.6.H2155.

  PMID: 8594927 BACKGROUND

• 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. doi: 10.1182/blood-2005-02-0567. Epub 2005 Mar 17.

  PMID: 15774613 BACKGROUND

• 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. doi: 10.1161/CIRCULATIONAHA.106.627091. Epub 2006 May 22.

  PMID: 16717147 BACKGROUND

• 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

  BACKGROUND

• 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. doi: 10.1038/ncpcardio0520. No abstract available.

  PMID: 16568110 BACKGROUND

• 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.

  BACKGROUND

• 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. doi: 10.1097/FJC.0b013e3180385ad7.

  PMID: 17513945 BACKGROUND

MeSH Terms

Conditions

Coronary Disease

Interventions

Amiloride; Nitrates; WW Domain-Containing Oxidoreductase; Clopidogrel; Aspirin; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Anions; Ions; Electrolytes; Inorganic Chemicals; Nitric Acid; Nitrogen Compounds; Organic Chemicals; Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Tumor Suppressor Proteins; Neoplasm Proteins; Proteins; Amino Acids, Peptides, and Proteins; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses

Study Officials

• Antonio J Delgado-Leon, MD

  University of Carabobo

  STUDY CHAIR

• Antonio R Delgado-Almeida, MD, FAHA, FACC, APS

  Clinical Research Unit at Docent Institute of Urology

  PRINCIPAL INVESTIGATOR

• Carlos L Delgado-Leon, MD

  Venezuelan Foundation of Heart Failure

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. of Medicine, MD

Study Record Dates

• First Submitted: October 29, 2010
• First Posted: November 1, 2010
• Study Start: February 1, 2009
• Primary Completion: May 1, 2010
• Study Completion: February 1, 2011
• Last Updated: June 11, 2012

Record last verified: 2012-04

Locations

VE (1)