SynthesisHypertension (Dallas, Tex. : 1979)2008
Pediatric antihypertensive trial failures: analysis of end points and dose range.
Synthesis in Hypertension (Dallas, Tex. : 1979), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 37 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Dose Rationale for Dapagliflozin and Empagliflozin in Paediatric Heart Failure: a Phase II.a Pharmacokinetics, Ease-of-swallow, Safety and Proof-of-concept Study Among Children 6-18 Years of Age
Methodological Improvement in Measuring Efficacy Outcome in Antihypertensive Trials in Children
Pediatric Hypertension and the Renin-Angiotensin SystEm (PHRASE): The Role of Angiotensin-(1-7) in Hypertension and Hypertension-Induced Heart and Kidney Damage
Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Pharmacological interventions for hypertension in children.The Cochrane database of systematic reviews · 2014Pooled it
- Racial differences in blood pressure response to angiotensin-converting enzyme inhibitors in children: a meta-analysis.Clinical pharmacology and therapeutics · 2008Pooled it
- Identifying and treating resistant hypertension in PRECISION: A randomized long-term clinical trial with aprocitentan.Journal of clinical hypertension (Greenwich, Conn.) · 2022Trial
- A physiologically based pharmacokinetic model for voriconazole disposition predicts intestinal first-pass metabolism in children.Clinical pharmacokinetics · 2014Trial
- Effectiveness and safety of valsartan in children aged 6 to 16 years with hypertension.Journal of clinical hypertension (Greenwich, Conn.) · 2011Trial
- Efficacy, safety, and pharmacokinetics of candesartan cilexetil in hypertensive children aged 6 to 17 years.Journal of clinical hypertension (Greenwich, Conn.) · 2008Trial
- Repurposing Empagliflozin for Duchenne Muscular Dystrophy-Associated Cardiomyopathy: Protocol for a Pharmacokinetics, Safety and Proof-of-Concept Trial in Children.Cardiology and therapy · 2026Article
- Dose Ranging in Pediatric Drug Development Trials Submitted to the US FDA 2012-2020.Journal of clinical pharmacology · 2025Article
- Empagliflozin in paediatric heart failure: model-based optimisation of a pharmacokinetic bridging study.Frontiers in medicine · 2025Article
- Challenges and Pitfalls: Performing Clinical Trials in Patients With Congenital Diaphragmatic Hernia.Frontiers in pediatrics · 2022Review
- Antihypertensive drugs use over a 5-year period among children and adolescents in Beijing, China: An observational study.Medicine · 2019Observational
- Rational Use of Medicine in Children-The Conflict of Interests Story. A Review.Rambam Maimonides medical journal · 2019Review
- Development of a Retinopathy of Prematurity Activity Scale and Clinical Outcome Measures for Use in Clinical Trials.JAMA ophthalmology · 2019Article
- Innovative Study Designs Optimizing Clinical Pharmacology Research in Infants and Children.Journal of clinical pharmacology · 2018Review
- Recommendations to Enhance Pediatric Cardiovascular Drug Development: Report of a Multi-Stakeholder Think Tank.Journal of the American Heart Association · 2018Article
- Effect of renal function on antihypertensive drug safety and efficacy in children.Pediatric nephrology (Berlin, Germany) · 2018Article
- Characteristics and Changes of Pediatric Therapeutic Trials under the Best Pharmaceuticals for Children Act.The Journal of pediatrics · 2018Article
- Development of Drug Therapies for Newborns and Children: The Scientific and Regulatory Imperatives.Pediatric clinics of North America · 2017Review
- Clinical Trial Design in Juvenile Idiopathic Arthritis.Paediatric drugs · 2017Article
- How to optimise drug study design: pharmacokinetics and pharmacodynamics studies introduced to paediatricians.The Journal of pharmacy and pharmacology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
Historically, drugs prescribed for children have not been studied in pediatric populations. Since 1997, however, a 6-month extension of marketing rights is granted if manufacturers conduct Food and Drug Administration-defined pediatric trials. In nearly half of the drugs studied, there were unexpected results in dosing, safety, or efficacy compared with adult studies, including failure of half of the antihypertensive dose-response trials, which are pivotal for deriving dosing recommendations. We sought to define design elements that might have contributed to these trial failures by combining patient-level data from 6 dose-ranging antihypertensive efficacy trials completed for pediatric exclusivity and submitted to the Food and Drug Administration from 1998 to 2005. We evaluated dosing, primary end point, and other components to assess underlying reasons for failure to show efficacy in children. Of 6 trials examined, 3 showed a dose response; 3 did not. Eligibility criteria were similar across studies, as were subject demographics. Successful studies showed large differences in doses, with little or no overlap between low, medium, and high doses; failed trials used narrow dose ranges with considerable overlap. Successful trials also provided pediatric formulations and used reduction in diastolic, not systolic, blood pressure as the primary end point. Careful attention to pediatric pharmacology and selection of primary end points can improve trial performance. We found poor dose selection, lack of acknowledgement of differences between adult and pediatric populations, and lack of pediatric formulations to be associated with failures. More importantly, our ability to combine data across trials allowed us to evaluate and potentially improve trial design.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.