ULTIMATE-SHF trial (UdenafiL Therapy to Improve symptoMAtology, exercise Tolerance and hEmodynamics in patients with chronic systolic heart failure): Study protocol for a randomized, placebo-controlled, double-blind trial

Trials

Volumn 14, Issue 1, 2013, Pages

  Kim, Kyung Hee ^a,b   Kim, Hyung Kwan ^a,b   Hwang, In Chang ^a,b   Lee, Seung Pyo ^a,b   Cho, Hyun Jai ^a,b   Kang, Hyun Jae ^a,b   Kim, Yong Jin ^a,b   Sohn, Dae Won ^a,b  

^a Seoul National University College of Medicine   (South Korea)

^b Seoul National University Hospital   (South Korea)

Author keywords

Chronic heart failure; Exercise capacity; Phosphodiesterase type 5 inhibitor; Udenafil

Indexed keywords

BRAIN NATRIURETIC PEPTIDE; CARBON DIOXIDE; PLACEBO; UDENAFIL;

ARTICLE; BREATHING; CARBON DIOXIDE EXCRETION; CARDIOVASCULAR MORTALITY; DIASTOLE; DRUG EFFICACY; FUNCTIONAL STATUS; HEART HEMODYNAMICS; HEART LEFT VENTRICLE CONTRACTION; HOSPITALIZATION; HUMAN; LUNG ARTERY PRESSURE; LUNG MINUTE VOLUME; OUTCOME ASSESSMENT; PROTEIN BLOOD LEVEL; RANDOMIZATION; RANDOMIZED CONTROLLED TRIAL (TOPIC); STUDY DESIGN; SYSTOLIC BLOOD PRESSURE; SYSTOLIC HEART FAILURE;

BIOLOGICAL MARKERS; CARDIOVASCULAR AGENTS; CHRONIC DISEASE; CLINICAL PROTOCOLS; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; EXERCISE TEST; EXERCISE TOLERANCE; HEART FAILURE, SYSTOLIC; HEMODYNAMICS; HOSPITALIZATION; HUMANS; NATRIURETIC PEPTIDE, BRAIN; OXYGEN CONSUMPTION; PHOSPHODIESTERASE 5 INHIBITORS; PROSPECTIVE STUDIES; PYRIMIDINES; RECOVERY OF FUNCTION; REPUBLIC OF KOREA; RESEARCH DESIGN; STROKE VOLUME; SULFONAMIDES; SYSTOLE; TIME FACTORS; TREATMENT OUTCOME; VENTRICULAR FUNCTION, LEFT;

EID: 84879102612     PISSN: None     EISSN: 17456215     Source Type: Journal    
DOI: 10.1186/1745-6215-14-188     Document Type: Article

References (31)

1. Eriksson H. Heart failure: a growing public health problem. J Internal Med 2009, 237:135-141.
2. Petrie M, Murray JM. Changes in notions about heart failure. Lancet 2001, 358:432-434. 10.1016/S0140-6736(01)05664-1, 11513900.
3. Ghio S, Gavazzi A, Campana C, Inserra C, Klersy C, Sebastiani R, Arbustini E, Recusani F, Tavazzi L. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol 2001, 37:183-188. 10.1016/S0735-1097(00)01102-5, 11153735.
4. Costard-Jäckle A, Fowler MB. Influence of preoperative pulmonary artery pressure on mortality after heart transplantation: testing of potential reversibility of pulmonary hypertension with nitroprusside is useful in defining a high risk group. J Am Coll Cardiol 1992, 19:48-54. 10.1016/0735-1097(92)90050-W, 1729345.
5. Cohen AH, Hanson K, Morris K, Fouty B, McMurty IF, Clarke W, Rodman DM. Inhibition of cyclic 3′5′-guanosine monophosphate-specific phosphodiesterase selectively vasodilates the pulmonary circulation in chronically hypoxic rats. J Clin Invest 1996, 97:172-179. 10.1172/JCI118386, 507076, 8550830.
6. Saraiva RM, Hare JM. Nitric oxide signaling in the cardiovascular system: implications for heart failure. Curr Opin Cardiol 2006, 21:221-228. 10.1097/01.hco.0000221584.56372.dc, 16601461.
7. Prasad S, Wilkinson J, Gatzoulis MA. Sildenafil in primary pulmonary hypertension. N Engl J Med 2000, 343:1342. 10.1056/NEJM200011023431814, 11183578.
8. Guazzi M, Tumminello G, Di Marco F, Fiorentini C, Guazzi MD. The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure. J Am Coll Cardiol 2004, 44:2339-2348. 10.1016/j.jacc.2004.09.041, 15607396.
9. Sastry BK, Narasimhan C, Reddy NK, Raju BS. Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized, placebo-controlled, double-blind, crossover study. J Am Coll Cardiol 2004, 43:1149-1153. 10.1016/j.jacc.2003.10.056, 15063421.
10. Lewis GD, Shah R, Shahzad K, Camuso JM, Pappagianopoulos PP, Hung J, Tawakol A, Gerszten RE, Systrom DM, Bloch KD, Semigran MJ. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation 2007, 116:1555-1562. 10.1161/CIRCULATIONAHA.107.716373, 17785618.
11. Salem EA, Kendirci M, Hellstrom WJ. Udenafil, a long-acting PDE5 inhibitor for erectile dysfunction. Curr Opin Investig Drugs 2006, 7:661-669.
12. Kim TE, Kim BH, Kim JR, Lim KS, Hong JH, Kim KP, Kim HS, Shin SG, Jang IJ, Yu KS. Effect of food on the pharmacokinetics of the oral phosphodiesterase 5 inhibitor udenafil for the treatment of erectile dysfunction. Br J Clin Pharmacol 2009, 68(1):43-6. 10.1111/j.1365-2125.2009.03404.x, 2732939, 19660002.
13. Kouvelas D, Goulas A, Papazisis G, Sardeli C, Pourzitaki C. PDE5 inhibitors: in vitro and in vivo pharmacological profile. Curr Pharm Des 2009, 15:3464-3475. 10.2174/138161209789206971, 19860692.
14. Paick JS, Kim SW, Yang DY, Kim JJ, Lee SW, Ahn TY, Choi HK, Suh JK, Kim SC. The efficacy and safety of udenafil, a new selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction. J Sex Med 2008, 5:946-953. 10.1111/j.1743-6109.2007.00723.x, 18221288.
15. Kang KK, Ahn GJ, Sohn YS, Ahn BO, Kim WB. DA-8159, a new PDE5 inhibitor, attenuates the development of compensatory right ventricular hypertrophy in a rat model of pulmonary hypertension. J Int Med Res 2003, 31:517-528. 10.1177/147323000303100608, 14708417.
16. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW. 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 2009, 119:e391-e479.
17. Kim BH, Lim HS, Chung JY, Kim JR, Lim KS, Sohn DR, Cho JY, Yu KS, Shin SG, Paick JS, Jang IJ. Safety, tolerability and pharmacokinetics of udenafil, a novel PDE-5 inhibitor, in healthy young Korean subjects. Br J Clin Pharmacol 2008, 65:848-854. 10.1111/j.1365-2125.2008.03107.x, 2485225, 18318773.
18. Park HJ, Park JK, Park K, Min K, Park NC. Efficacy of udenafil for the treatment of erectile dysfunction up to 12 hours after dosing: a randomized placebo-controlled trial. J Sex Med 2010, 7:2209-2216. 10.1111/j.1743-6109.2010.01817.x, 20412426.
19. Balady GJ, Arena R, Sietsema K, Myers J, Coke L, Fletcher GF, Forman D, Franklin B, Guazzi M, Gulati M, Keteyian SJ, Lavie CJ, Macko R, Mancini D, Milani RV. Clinician's Guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association. Circulation 2010, 122:191-225. 10.1161/CIR.0b013e3181e52e69, 20585013.
20. Froelicher VF, Myers JN. Interpretation of hemodynamic responses to exercise testing. Exercise and the Heart 2000, 93-120. Philadelphia, PA: WB Saunders, Froelicher VF, Myers JN, 4.
21. Beaver WL, Wasserman K, Whipp BJ. A new method for detecting anaerobic threshold by gas exchange. J Appl Physiol 1986, 60:2020-2027.
22. Guazzi M, Vicenzi M, Arena R, Guazzi MD. PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study. Circ Heart Fail 2011, 4:8-17. 10.1161/CIRCHEARTFAILURE.110.944694, 21036891.
23. Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 1988, 333:664-666. 10.1038/333664a0, 3131684.
24. Guazzi M, Samaja M. The role of PDE5-inhibitors in cardiopulmonary disorders: from basic evidence to clinical development. Curr Med Chem 2007, 14:2181-2191. 10.2174/092986707781389619, 17691956.
25. Nagendran J, Archer SL, Soliman D, Gurtu V, Moudgil R, Haromy A, St Aubin C, Webster L, Rebeyka IM, Ross DB, Light PE, Dyck JR, Michelakis ED. Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation 2007, 116:238-248. 10.1161/CIRCULATIONAHA.106.655266, 17606845.
26. Bocchi EA, Guimaraes G, Mocelin A, Bacal F, Bellotti G, Ramires JF. Sildenafil effects on exercise, neurohormonal activation, and erectile dysfunction in congestive heart failure: a double-blind, placebo-controlled, randomized study followed by a prospective treatment for erectile dysfunction. Circulation 2002, 106:1097-1103. 10.1161/01.CIR.0000027149.83473.B6, 12196335.
27. Teixeira CE, Priviero FB, Webb RC. Differential effects of the phosphodiesterase type 5 inhibitors sildenafil, vardenafil, and tadalafil in rat aorta. J Pharmacol Exp Ther 2006, 316:654-661.
28. Padma-Nathan H, Stecher VJ, Sweeney M, Orazem J, Tseng LJ, Deriesthal H. Minimal time to successful intercourse after sildenafil citrate: results of a randomized, double-blind, placebo-controlled trial. Urology 2003, 62:400-403. 10.1016/S0090-4295(03)00567-3, 12946731.
29. Walker DK, Ackland MJ, James GC, Muirhead GJ, Rance DJ, Wastall P, Wright PA. Pharmacokinetics and metabolism of sildenafil in mouse, rat, rabbit, dog and man. Xenobiotica 1999, 29:297-310. 10.1080/004982599238687, 10219969.
30. Frishman WH. Importance of medication adherence in cardiovascular disease and the value of once-daily treatment regimens. Cardiol Rev 2007, 15:257-263. 10.1097/CRD.0b013e3180cabbe7, 17700384.
31. Fitzgerald AA, Powers JD, Ho PM, Maddox TM, Peterson PN, Allen LA, Masoudi FA, Magid DJ, Havranek EP. Impact of medication nonadherence on hospitalizations and mortality in heart failure. J Card Fail 2011, 17:664-669. 10.1016/j.cardfail.2011.04.011, 21807328.