BACKGROUND: Mitral regurgitation is the most common indication for reoperation in children following repair of atrioventricular septal defect (AVSD). We hypothesized that angiotensin-converting enzyme inhibitor therapy would decrease the severity of mitral regurgitation and limit left ventricular volume overload in children following AVSD repair. METHODS: The Pediatric Heart Network designed a placebo-controlled randomized trial of enalapril in this population. The primary aim was to test the effect of enalapril on the change in left ventricular end-diastolic dimension body surface area-adjusted z score. Before the launch of the trial, a feasibility study was performed to estimate the number of patients with at least moderate mitral regurgitation following AVSD repair. TRIAL EXPERIENCE: Seventeen months after the start of the study, 349 patients were screened, 8 were trial eligible, and only 5 were enrolled. The study was subsequently terminated because of low patient accrual. Several factors led to the problems with patient accrual, including (1) the use of criteria to assess disease severity in the feasibility study that were not identical to those used in the trial, (2) failure to achieve equipoise for the study among clinicians and referring physicians, (3) reliance on methodology developed in adult populations with different disease mechanisms, and (4) absence of adequate data to define the natural history of the disease process under study. Progress in the treatment of children with cardiovascular disease will depend on the future of multicenter collaborative clinical trials. The lessons learned from this study may contribute to improvements in this research.
RCT Entities:
BACKGROUND:Mitral regurgitation is the most common indication for reoperation in children following repair of atrioventricular septal defect (AVSD). We hypothesized that angiotensin-converting enzyme inhibitor therapy would decrease the severity of mitral regurgitation and limit left ventricular volume overload in children following AVSD repair. METHODS: The Pediatric Heart Network designed a placebo-controlled randomized trial of enalapril in this population. The primary aim was to test the effect of enalapril on the change in left ventricular end-diastolic dimension body surface area-adjusted z score. Before the launch of the trial, a feasibility study was performed to estimate the number of patients with at least moderate mitral regurgitation following AVSD repair. TRIAL EXPERIENCE: Seventeen months after the start of the study, 349 patients were screened, 8 were trial eligible, and only 5 were enrolled. The study was subsequently terminated because of low patient accrual. Several factors led to the problems with patient accrual, including (1) the use of criteria to assess disease severity in the feasibility study that were not identical to those used in the trial, (2) failure to achieve equipoise for the study among clinicians and referring physicians, (3) reliance on methodology developed in adult populations with different disease mechanisms, and (4) absence of adequate data to define the natural history of the disease process under study. Progress in the treatment of children with cardiovascular disease will depend on the future of multicenter collaborative clinical trials. The lessons learned from this study may contribute to improvements in this research.
Authors: Daniel K Benjamin; Philip Brian Smith; M Dianne Murphy; Rosemary Roberts; Lisa Mathis; Debbie Avant; Robert M Califf; Jennifer S Li Journal: JAMA Date: 2006-09-13 Impact factor: 56.272
Authors: R O Bonow; B Carabello; A C de Leon; L H Edmunds; B J Fedderly; M D Freed; W H Gaasch; C R McKay; R A Nishimura; P T O'Gara; R A O'Rourke; S H Rahimtoola; J L Ritchie; M D Cheitlin; K A Eagle; T J Gardner; A Garson; R J Gibbons; R O Russell; T J Ryan; S C Smith Journal: J Heart Valve Dis Date: 1998-11
Authors: A Derk Jan Ten Harkel; Adri H Cromme-Dijkhuis; Bianca C C Heinerman; Wim C Hop; Ad J J C Bogers Journal: Ann Thorac Surg Date: 2005-02 Impact factor: 4.330
Authors: L Mahony; L A Sleeper; P A W Anderson; W M Gersony; B W McCrindle; L L Minich; J W Newburger; J P Saul; V L Vetter; G D Pearson Journal: Pediatr Cardiol Date: 2006 Mar-Apr Impact factor: 1.655
Authors: F L Hanley; K N Fenton; R A Jonas; J E Mayer; N R Cook; G Wernovsky; A R Castaneda Journal: J Thorac Cardiovasc Surg Date: 1993-09 Impact factor: 5.209
Authors: Michelle S Hamstra; Victoria L Pemberton; Nicholas Dagincourt; Danielle Hollenbeck-Pringle; Felicia L Trachtenberg; James F Cnota; Andrew M Atz; Elizabeth Cappella; Sylvia De Nobele; Josephine Grima; Martha King; Rosalind Korsin; Linda M Lambert; Meghan K MacNeal; Larry W Markham; Gretchen MacCarrick; Donna M Sylvester; Patricia Walter; Mingfen Xu; Ronald V Lacro Journal: Clin Trials Date: 2020-08-21 Impact factor: 2.486
Authors: Sara K Pasquali; Jonathan R Kaltman; J William Gaynor; Brian W McCrindle; Jane W Newburger; Brett R Anderson; Mark A Scheurer; Nelangi M Pinto; Jeffrey B Anderson; Matthew E Oster; Jeffrey P Jacobs; Bradley S Marino; Carlos M Mery; Gail D Pearson Journal: Cardiol Young Date: 2019-08-06 Impact factor: 1.093
Authors: Emmeline E Calkoen; Jos J M Westenberg; Lucia J M Kroft; Nico A Blom; Mark G Hazekamp; Marry E Rijlaarsdam; Monique R M Jongbloed; Albert de Roos; Arno A W Roest Journal: J Cardiovasc Magn Reson Date: 2015-02-19 Impact factor: 5.364
Authors: Christoph P Hornik; Patricia Y Chu; Jennifer S Li; Reese H Clark; Phillip Brian Smith; Kevin D Hill Journal: Pediatr Crit Care Med Date: 2014-11 Impact factor: 3.971