Pediatric cardiovascular drug trials, lessons learned

Journal of Cardiovascular Pharmacology

Volumn 58, Issue 1, 2011, Pages 4-8

  Li, Jennifer S ^a   Cohen Wolkowiez, Michael ^a   Pasquali, Sara K ^a  

^a DUKE CLINICAL RESEARCH INSTITUTE   (United States)

Author keywords

clinical trials; congenital heart disease; pediatric

Indexed keywords

AMLODIPINE; CARDIOVASCULAR AGENT; CARVEDILOL; CLOPIDOGREL; ENALAPRIL; ENOXAPARIN; FOSINOPRIL; IRBESARTAN; LISINOPRIL; LOSARTAN; MILRINONE; PLACEBO; SILDENAFIL; SOTALOL; VALSARTAN;

BLOOD PRESSURE; CHILD; CLINICAL TRIAL (TOPIC); CONGENITAL HEART DISEASE; CREATININE CLEARANCE; DEEP VEIN THROMBOSIS; DIASTOLIC BLOOD PRESSURE; DOSE RESPONSE; DRUG ABSORPTION; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE COMPARISON; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG FORMULATION; DRUG MEGADOSE; DRUG METABOLISM; DRUG MONITORING; DRUG STABILITY; DRUG TOLERANCE; EQUIPOISE; FLAVOR; HEART FAILURE; HEART LEFT VENTRICLE OVERLOAD; HUMAN; HYPERTENSION; LOW DRUG DOSE; MITRAL VALVE REGURGITATION; PILL; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; STUDY DESIGN; TASTE; TREATMENT OUTCOME;

AGE FACTORS; BIOLOGICAL MARKERS; CARDIOVASCULAR AGENTS; CARDIOVASCULAR DISEASES; CHILD; CLINICAL TRIALS AS TOPIC; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS;

EID: 79960391881     PISSN: 01602446     EISSN: 15334023     Source Type: Journal    
DOI: 10.1097/FJC.0b013e31820d1c54     Document Type: Review

References (32)

1. Lee PY, Alexander KP, Hammill BG, et al. Representation of elderly persons and women in published randomized trials of acute coronary syndromes. JAMA. 2001;286:708-713. (Pubitemid 33010364)
2. Heiat A, Gross CP, Krumholz HM. Representation of the elderly, women, and minorities in heart failure clinical trials. Arch Intern Med. 2002;162: 1682-1688.
3. Shah SS, Hall M, Goodman D, et al. Off-label drug use in hospitalized children. Arch Pediatr Adolesc Med. 2007;161:282-290. (Pubitemid 46364332)
4. Pasquali SK, Hall M, Slonim AD, et al. Off-label use of cardiovascular medications in children hospitalized with congenital and acquired heart disease. Circ Cardiovasc Qual Outcomes. 2008:1:74-83.
5. Mahony L, Sleeper LA, Anderson PA, et al. The Pediatric Heart Network: a primer for the conduct of multicenter studies in children with congenital and acquired heart disease. Pediatr Cardiol. 2006;27:191-198.
6. Pawar S, Kumar A. Issues in the formulation of drugs for oral use in children: role of excipients. Pediatr Drugs. 2002;4:371-379. (Pubitemid 34651926)
7. Saul JP, Ross B, Schaffer MS, et al. Pharmacokinetics and pharmacodynamics of sotalol in a pediatric population with supraventricular and ventricular tachyarrhythmia. Clin Pharmacol Ther. 2001;69:145-157. (Pubitemid 32225415)
8. Li JS, Yow E, Berezny KY, et al. Dosing of clopidogrel for platelet inhibition in infants and young children: primary results of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) trial. Circulation. 2008;117:553-559.
9. Monagle P, Chan A, Massicotte P, et al. Antithrombotic therapy in children: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 suppl):645S-687S. (Pubitemid 39297967)
10. Ignjatovic V, Najid S, Newall F, et al. Dosing and monitoring of enoxaparin (Low molecular weight heparin) therapy in children. Br J Haematol. 2010;149:734-738. E-pub March 21, 2010.
11. Flynn JT, Newburger JW, Daniels SR, et al. A randomized, placebocontrolled trial of amlodipine in children withhypertension. J Pediatr. 2004;145:353-359. (Pubitemid 39165684)
12. Sorof JM, Cargo P, Graepel J, et al. Beta-blocker/thiazide combination for treatment of hypertensive children: a randomized double-blind, placebocontrolled trial. Pediatr Nephrol. 2002;17:345-350. (Pubitemid 36076050)
13. Trachtman H, Hainer JW, Sugg J, et al, and Candesartan in Children with Hypertension (CINCH) Investigators. Efficacy, safety, and pharmacokinetics of candesartan cilexetil in hypertensive children aged 6 to 17 years. J Clin Hypertens (Greenwich). 2008;10:743-750.
14. Wells T, Frame V, Soffer B, et al. A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of enalapril for children with hypertension. J Clin Pharmacol. 2002;42:870-880. (Pubitemid 34803850)
15. Li JS, Flynn JT, Portman R, et al. The efficacy and safety of the novel aldosterone antagonist eplerenone in hypertensive children: a randomized, double-blind dose-response study. J Pediatr. 2010;157:282-287.
16. Trachtman H, Frank R, Mahan JD, et al. Clinical trial of extended-release felodipine in pediatric essential hypertension. Pediatr Nephrol. 2003;18: 548-553. (Pubitemid 36790096)
17. Li JS, Berezny K, Kilaru R, et al. Is the extrapolated adult dose of fosinopril safe and effective in treating hypertensive children? Hypertension. 2004;44:289-293. (Pubitemid 39167224)
18. Sakarcan A, Tenney F, Wilson JT, et al. The pharmacokinetics of irbesartan in hypertensive children and adolescents. J Clin Pharmacol. 2001;41:742-749. (Pubitemid 32612437)
19. Soffer B, Zhang Z, Miller K, et al. A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of lisinopril for children with hypertension. Am J Hypertens. 2003;16:795-800. (Pubitemid 37204674)
20. Shahinfar S, Cano F, Soffer BA, et al. A double-blind, dose-response study of losartan in hypertensive children. Am J Hypertens. 2005;18: 183-190. (Pubitemid 40332547)
21. Batisky DL, Sorof JM, Sugg J, et al, and Toprol-XL Pediatric Hypertension Investigators. Efficacy and safety of extended release metoprolol succinate in hypertensive children 6 to 16 years of age: a clinical trial experience. J Pediatr. 2007;150:134-139, 139.e1.
22. Blumer JL, Daniels SR, Dreyer WJ, et al. Pharmacokinetics of quinapril in children: assessment during substitution for chronic angiotensin-converting enzyme inhibitor treatment. J Clin Pharmacol. 2003;43:128-132. (Pubitemid 36125938)
23. Flynn JT, Meyers KEC, Neto JP, et al, For the Pediatric Valsartan Study Group. Efficacy and safety of the angiotensin receptor blocker valsartan in children with hypertension aged 1 to 5 years. Hypertension. 2008;52: 222-228.
24. Freedman B. Equipoise and the ethics of clinical research. N Engl J Med. 1987;317:141-145. (Pubitemid 17092151)
25. Minich LL, Atz AM, Colan SD, et al. Partial and transitional atrioventricular septal defect outcomes: does age at repair matter? Ann Thorac Surg. 2010;89:530-536.
26. Benjamin DK Jr, Smith PB, Jadhav P, et al. Pediatric antihypertensive trial failures: analysis of endpoints and dose range. Hypertension. 2008;51: 834-840. (Pubitemid 351654692)
27. Walker EP. FDA Panel Grapples with Changing Study Endpoint. Available at: http://www.medpagetoday.com/PublicHealthPolicy/FDA General/21423. Accessed October 31, 2010.
28. Hsu DT, Zak V, Mahony L, et al, and Pediatric Heart Network Investigators. Enalapril in infants with single ventricle: results of a multicenter randomized trial. Circulation. 2010;122:333-340.
29. Hoffman TM, Wernovsky G, Atz AM, et al. Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation. 2003;107:996-1002. (Pubitemid 36258723)
30. Shaddy RE, Boucek MM, Hsu DT, et al, and Pediatric Carvedilol Study Group. Carvedilol for children and adolescents with heart failure: a randomized controlled trial. JAMA. 2007;298:1171-1179. (Pubitemid 47403103)
31. Wessel DL, Berger F, Li JS, et al, For the CLARINET Investigators. A Randomized Trial of Clopidogrel to Reduce Mortality and Shunt-Related Morbidity in Infants Palliated with a Systemic to Pulmonary Artery Shunt. American Heart Association 2010 Scientific Sessions. Available at: http://www. scientificsessions-365.com/highlight.aspx?id=2272&p=202. Accessed February 7, 2011.
32. Roberts R, Rodriguez W, Murphy D, et al. Pediatric drug labeling: improving the safety and efficacy of pediatric therapies. JAMA. 2003;290: 905-911. (Pubitemid 37430462)