Evidence map›Paper›PMID 31312867›Full record

Trial reportEuropean journal of clinical pharmacology2019

Dose rationale and pharmacokinetics of dexmedetomidine in mechanically ventilated new-borns: impact of design optimisation.

Sven C van Dijkman, Pieter A J G De Cock, Koenraad Smets, Wim Decaluwe, Anne Smits, Karel Allegaert, Johan Vande Walle, Peter De Paepe, Oscar Della Pasqua

Open access · hybridAbstract readClinical Trial
PubMed Publisher
In one paragraph

Trial report in European journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 7% of its field
1 · What the graph read from 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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 6 institutions in 3 countries.

Sven C van DijkmanDivision of Pharmacology, Leiden Academic Centre for Drug Research, Leiden, The Netherlands.
Pieter A J G De CockHeymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
Koenraad SmetsDepartment of Neonatology, Ghent University Hospital, Ghent, Belgium.
Wim DecaluweDepartment of Neonatology, AZ Sint Jan Brugge-Oostende AV, Bruges, Belgium.
Anne SmitsNeonatal Intensive Care Unit, University Hospital Leuven, Leuven, Belgium.
Karel AllegaertIntensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
Johan Vande WalleDepartment of Paediatric Nephrology, Ghent University Hospital, Ghent, Belgium.
Peter De PaepeHeymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
Oscar Della PasquaClinical Pharmacology and Therapeutics, University College London, BMA House, Tavistock Square, London, WC1H 9JP, UK. o.dellapasqua@ucl.ac.uk.
Ghent University · BEGhent University Hospital · BEKU Leuven · BEAZ Sint-Jan · BECentre for Human Drug Research · NLUniversity College London · GB

Funding

Agentschap voor Innovatie door Wetenschap en Technologie IWT/SBO/130033FP7 International Cooperation 261060Universitair Ziekenhuis Gent WR/1492/APO/001
6 · The paper itself

Abstract

purposeThere is a need for alternative analgosedatives such as dexmedetomidine in neonates. Given the ethical and practical difficulties, protocol design for clinical trials in neonates should be carefully considered before implementation. Our objective was to identify a protocol design suitable for subsequent evaluation of the dosing requirements for dexmedetomidine in mechanically ventilated neonates.

methodsA published paediatric pharmacokinetic model was used to derive the dosing regimen for dexmedetomidine in a first-in-neonate study. Optimality criteria were applied to optimise the blood sampling schedule. The impact of sampling schedule optimisation on model parameter estimation was assessed by simulation and re-estimation procedures for different simulation scenarios. The optimised schedule was then implemented in a neonatal pilot study.

resultsParameter estimates were more precise and similarly accurate in the optimised scenarios, as compared to empirical sampling (normalised root mean square error: 1673.1% vs. 13,229.4% and relative error: 46.4% vs. 9.1%). Most importantly, protocol deviations from the optimal design still allowed reasonable parameter estimation. Data analysis from the pilot group (n = 6) confirmed the adequacy of the optimised trial protocol. Dexmedetomidine pharmacokinetics in term neonates was scaled using allometry and maturation, but results showed a 20% higher clearance in this population compared to initial estimates obtained by extrapolation from a slightly older paediatric population. Clearance for a typical neonate, with a post-menstrual age (PMA) of 40 weeks and weight 3.4 kg, was 2.92 L/h. Extension of the study with 11 additional subjects showed a further increased clearance in pre-term subjects with lower PMA.

conclusionsThe use of optimal design in conjunction with simulation scenarios improved the accuracy and precision of the estimates of the parameters of interest, taking into account protocol deviations, which are often unavoidable in this event-prone population.

Indexed as

Models, BiologicalAnalgesics, Non-NarcoticDexmedetomidineFemaleHumansHypnotics and SedativesInfant, NewbornInfant, PrematureMaleRespiration, ArtificialAnalgesics, Non-NarcoticDexmedetomidineHypnotics and SedativesClinical trial simulationsDexmedetomidineDose rationaleExtrapolationOptimal designPaediatricsPharmacokinetic modellingSparse sampling

Identifiers

PMID31312867
OpenAlexW2956645472

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.