1 / 28

Current Clinical Trials in AKI – What Questions Are They Addressing?

Current Clinical Trials in AKI – What Questions Are They Addressing?. Sean M Bagshaw, MD, MSc Division of Critical Care Medicine Faculty of Medicine and Dentistry, University of Alberta 1 st International Symposium on AKI in Children Cincinnati, Ohio September 28, 2012. Disclosure Summary.

frey
Download Presentation

Current Clinical Trials in AKI – What Questions Are They Addressing?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Current Clinical Trials in AKI – What Questions Are They Addressing? Sean M Bagshaw, MD, MSc Division of Critical Care Medicine Faculty of Medicine and Dentistry, University of Alberta 1st International Symposium on AKI in Children Cincinnati, Ohio September 28, 2012

  2. Disclosure Summary • Sean M Bagshaw, MD, MSc • Consultancy: Gambro Inc. • Speaking: Gambro Inc., Alere Inc.

  3. Learning Objectives • Review Current Clinical Trials in AKI • Adult • Pediatric • Discuss Barriers to Trials in Children • Future Directions

  4. Search of ClinicalTrials.gov - 126 clinical trials • Adult trials ~ 118 (93.6%) • Pediatric trials ~ 8 (6.4%) → now 10 (updated) Faubel et al CJASN 2012

  5. Current Pediatric Clinical Trials

  6. Current Pediatric Clinical Trials

  7. Barriers to Evidence in Kids • Challenges with INFORMED CONSENT • Novel methods (i.e. staged consent procedures) • Multi-factorial assessments of competence • Paucity of dedicated FUNDING to pediatric AKI • Smaller “market” size – less industry interest Faubel et al CJASN 2012

  8. Barriers to Evidence in Kids • Need for specialized DOSING/FORMULATIONS • Limited “at-risk” population – trial design/logistics • FEWER CHILDREN with disease • FEWER OUTCOME EVENTS (RRT, death) • Often EXCLUDED from ADULT randomized trials

  9. Barriers to Evidence in Kids • CHILDREN are “under-studied” • 8/118 (6.4%) of AKI-related trials listed on ClinicalTrials.gov involved children • Implications/consequences: • Lack of data on efficacy/safety of interventions • Off label use common (extrapolation from adults) • Arguably UNETHICALto exclude children in randomized trials focused on AKI (and in general) • MISSED OPPORTUNITY

  10. 9 topics with statistically significant discrepancies, 4 clinically important: • Arteminisnin vs. quinine for severe malaria (↑ survival in adults, not children) • Phenobarb in cerebral malaria (↑ survival in adults, ↑ mortality in children) • Long-acting β-agonist in asthma (↓ exacerbation in adults, not children) • Corticosteroids in meningitis (↑ survival in adults, not children) Are the results of ADULT trials concordant with PEDIATRIC trials? Ioannidis et al J Pediatr 2010

  11. Children Adults

  12. Adult/Pediatric Collaboration • Critical Illness – Focused Interventions: • Resuscitation in Sepsis • Corticosteroids in Sepsis • Extracorporeal support • Traumatic brain injury

  13. Population: Adults patients admitted to ICU with DKA (n=23) • Design: Retrospective cohort study • Exposure: Resuscitation with PL vs. NS in first 12 hr Chua et al J Crit Care 2012

  14. Australasian Resuscitation In Sepsis Evaluation • Design: Multi-national, multi-centre (45), randomized, controlled trial • Population: Adult patients with severe sepsis presenting to the ED • Intervention: EGDT compared to standard-of-care • Target Recruitment: 1600 patients (800 in each arm)

  15. Australasian Resuscitation In Sepsis Evaluation (UK Study) – 47 sites - started Feb 2011 – recruitment goal 1260 adult septic patients (n=515) (US Study) – 26 sites - started Mar 2008 – recruitment goal 1900 adult septic patients (n=1161)

  16. Adult/Pediatric Collaboration • AKI – Focused Interventions: • Prevention of CSA-AKI* • Acetaminophen • Fenoldopam • RIPC • Tight glycemic control • Rewarming • Prevention of CKD after AKI • Optimal timing of RRT initiation • Blood purification in Sepsis/MODS * Currently duplicate trials in children + adults

  17. n=10 Nguyen et al CCM 2008

  18. Valentine et al CCM 2012

  19. Valentine et al CCM 2012

  20. NGAL-Directed RRT Initiation Use of Neutrophil Gelatinase-Associated Lipocalin (NGAL) to Optimize Fluid Dosing, Continuous Renal Replacement Therapy (CRRT) Initiation and Discontinuation in Critically Ill Children With Acute Kidney Injury (AKI) ClinicalTrials.gov Identifier: NCT01416298 Available at: http://www.clinicaltrials.gov/ct2/show/NCT01416298?term=NCT01416298&rank=1

  21. NGAL-Directed RRT Initiation Hypotheses: • ↑ NGAL will predict >10% fluid overload (FO) • ↑ NGAL will predict, in children with 10-20% FO, no improvement or worsening AKI in 24-48 hr → Decision support to start RRT • ↓ NGAL will be associated with improvement in urine output and initial resolution of AKI in <72 hr → Decision support to stop RRT Available at: http://www.clinicaltrials.gov/ct2/show/NCT01416298?term=NCT01416298&rank=1

  22. The STARRT-AKIStudy: STandard versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury ClinicalTrials.gov Identifier: NCT01557361

  23. The SPARK Study: A randomized controlled trial of furoSemide in critically ill Patients with eARly acute Kidney injury ClinicalTrials.gov Identifier: NCT00978354

  24. Thank You For Your Attention! • Acknowledgements • Stuart Goldstein Questions? bagshaw@ualberta.ca

More Related