BACKGROUND: Casual office blood pressure (CBP) measurements are still standard in antihypertensive drug trials. In pediatric hypertensive trials, ethical considerations, very low disease prevalence and the marked impact of white-coat hypertension create the need for very sensitive and reproducible techniques of BP assessment. We hypothesized that ambulatory BP monitoring (ABPM) may identify treatment effects more sensitively than CBP and thereby reduce sample sizes required in pediatric antihypertensive trials. METHODS: Standard deviations (SDs) were used to assess population variability of CBP and ABPM at baseline and after 6 months standardized antihypertensive treatment from a trial investigating the BP-lowering effect of ramipril in children with chronic kidney disease. RESULTS: In 157 hypertensive children, ramipril had a similar mean BP-lowering effect on clinic and ambulatory 24-h BP for systolic (-10 vs. -11 mmHg, P = NS) and diastolic values (-9 vs. -11 mmHg, P = NS). However, the SDs of the CBP responses were up to 39% larger than those of ABPM (SBP 15.5 vs. 9.4; DBP 13.8 vs. 8.8; both P < 0.0001). Using power analysis, we demonstrate that, depending on the magnitude of the expected antihypertensive effect and trial design, the utilization of ABPM in antihypertensive drug efficacy studies allows reduction of sample sizes by 57-75%. This reduction of cohort size with ABPM is substantially greater than previously observed for adults. CONCLUSION: The primary use of ABPM can substantially reduce the number of children put at potential risk in blinded antihypertensive drug trials by up to three quarters.
BACKGROUND: Casual office blood pressure (CBP) measurements are still standard in antihypertensive drug trials. In pediatric hypertensive trials, ethical considerations, very low disease prevalence and the marked impact of white-coat hypertension create the need for very sensitive and reproducible techniques of BP assessment. We hypothesized that ambulatory BP monitoring (ABPM) may identify treatment effects more sensitively than CBP and thereby reduce sample sizes required in pediatric antihypertensive trials. METHODS: Standard deviations (SDs) were used to assess population variability of CBP and ABPM at baseline and after 6 months standardized antihypertensive treatment from a trial investigating the BP-lowering effect of ramipril in children with chronic kidney disease. RESULTS: In 157 hypertensivechildren, ramipril had a similar mean BP-lowering effect on clinic and ambulatory 24-h BP for systolic (-10 vs. -11 mmHg, P = NS) and diastolic values (-9 vs. -11 mmHg, P = NS). However, the SDs of the CBP responses were up to 39% larger than those of ABPM (SBP 15.5 vs. 9.4; DBP 13.8 vs. 8.8; both P < 0.0001). Using power analysis, we demonstrate that, depending on the magnitude of the expected antihypertensive effect and trial design, the utilization of ABPM in antihypertensive drug efficacy studies allows reduction of sample sizes by 57-75%. This reduction of cohort size with ABPM is substantially greater than previously observed for adults. CONCLUSION: The primary use of ABPM can substantially reduce the number of children put at potential risk in blinded antihypertensive drug trials by up to three quarters.
Authors: Laura Massella; Djalila Mekahli; Dušan Paripović; Larisa Prikhodina; Nathalie Godefroid; Anna Niemirska; Ayşe Ağbaş; Karolina Kalicka; Augustina Jankauskiene; Malgorzata Mizerska-Wasiak; Alberto Caldas Afonso; Rémi Salomon; Georges Deschênes; Gema Ariceta; Z Birsin Özçakar; Ana Teixeira; Ali Duzova; Jérôme Harambat; Tomáš Seeman; Gabriela Hrčková; Adrian Catalin Lungu; Svetlana Papizh; Amira Peco-Antic; Stéphanie De Rechter; Ugo Giordano; Marietta Kirchner; Teresa Lutz; Franz Schaefer; Olivier Devuyst; Elke Wühl; Francesco Emma Journal: Clin J Am Soc Nephrol Date: 2018-04-19 Impact factor: 8.237