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Original research article
Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients: a phase 2 randomised clinical trial
  1. Thomas Engstrøm1,2,
  2. Lars Nepper-Christensen1,
  3. Steffen Helqvist1,
  4. Lene Kløvgaard1,
  5. Lene Holmvang1,
  6. Erik Jørgensen1,
  7. Frants Pedersen1,
  8. Kari Saunamaki1,
  9. Hans-Henrik Tilsted1,
  10. Adam Steensberg3,
  11. Søren Fabricius3,
  12. Ulrik Mouritzen3,
  13. Niels Vejlstrup1,
  14. Kiril A Ahtarovski1,
  15. Christoffer Göransson1,
  16. Litten Bertelsen1,
  17. Kasper Kyhl1,
  18. Göran Olivecrona2,
  19. Henning Kelbæk4,
  20. Jens Flensted Lassen1,
  21. Lars Køber1,
  22. Jacob Lønborg1
  1. 1Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  2. 2Department of Cardiology, University of Lund, Lund, Sweden
  3. 3Zealand Pharma A/S, Copenhagen, Denmark
  4. 4Department of Cardiology, Zealand University Hospital, Roskilde, Denmark
  1. Correspondence to Professor Thomas Engstrøm, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark ; thomas.engstroem{at}regionh.dk

Abstract

Objectives Reperfusion immediately after reopening of the infarct-related artery in ST-segment elevation myocardial infarction (STEMI) may cause myocardial damage in addition to the ischaemic insult (reperfusion injury). The gap junction modulating peptide danegaptide has in animal models reduced this injury. We evaluated the effect of danegaptide on myocardial salvage in patients with STEMI.

Methods In addition to primary percutaneous coronary intervention in STEMI patients with thrombolysis in myocardial infarction flow 0–1, single vessel disease and ischaemia time less than 6 hours, we tested, in a clinical proof-of-concept study, the therapeutic potential of danegaptide at two-dose levels. Primary outcome was myocardial salvage evaluated by cardiac MRI after 3 months.

Results From November 2013 to August 2015, a total of 585 patients were randomly enrolled in the trial. Imaging criteria were fulfilled for 79 (high dose), 80 (low dose) and 84 (placebo) patients eligible for the per-protocol analysis. Danegaptide did not affect the myocardial salvage index (danegaptide high (63.9±14.9), danegaptide low (65.6±15.6) and control (66.7±11.7), P=0.40), final infarct size (danegaptide high (19.6±11.4 g), danegaptide low (18.6±9.6 g) and control (21.4±15.0 g), P=0.88) or left ventricular ejection fraction (danegaptide high (53.9%±9.5%), danegaptide low (52.7%±10.3%) and control (52.1%±10.9%), P=0.64). There was no difference between groups with regard to clinical outcome.

Conclusions Administration of danegaptide to patients with STEMI did not improve myocardial salvage.

Trial registration number NCT01977755; Pre-results.

  • cardiac magnetic resonance (cmr) imaging
  • percutaneous coronary intervention
  • acute myocardial infarction

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Footnotes

  • Contributors Planning: TE, LK, NV, KAA, JL, LN-C, AS, SF and UM. Conduct and reporting: all authors. Overall responsible: TE.

  • Funding Zealand Pharma A/S, Denmark funded the study and supplied the study drug.

  • Competing interests TE reports personal fees from Bayer, personal fees from St. Jude Medical, personal fees from Boston Scientific, personal fees from Medtronic, outside the submitted work and consultant fee and research grant from Zealand. JFL reports grants from St. Jude Medical/Abbott, personal fees from Biosensors, grants from Boston Scientific, grants from Biotronik, outside the submitted work. LK reports personal fees from Novartis as speaker, outside the submitted work. JL reports personal fees from St. Jude Medical, outside the submitted work.

  • Patient consent Not required.

  • Ethics approval The trial was approved by the Independent Ethics Committee and the Danish Health and Medicines Agency (DHMA; Jour. No.: 2013102384).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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