Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients: a phase 2 randomised clinical trial

Thomas Engstrøm; Lars Nepper-Christensen; Steffen Helqvist; Lene Kløvgaard; Lene Holmvang; Erik Jørgensen; Frants Pedersen; Kari Saunamaki; Hans-Henrik Tilsted; Adam Steensberg; Søren Fabricius; Ulrik Mouritzen; Niels Vejlstrup; Kiril A Ahtarovski; Christoffer Göransson; Litten Bertelsen; Kasper Kyhl; Göran Olivecrona; Henning Kelbæk; Jens Flensted Lassen; Lars Køber; Jacob Lønborg

doi:10.1136/heartjnl-2017-312774

Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients: a phase 2 randomised clinical trial

Thomas Engstrøm, Lars Nepper-Christensen, Steffen Helqvist, Lene Kløvgaard, Lene Holmvang, Erik Jørgensen, Frants Pedersen, Kari Saunamaki, Hans-Henrik Tilsted, Adam Steensberg, Søren Fabricius, Ulrik Mouritzen, Niels Vejlstrup, Kiril A Ahtarovski, Christoffer Göransson, Litten Bertelsen, Kasper Kyhl, Göran Olivecrona, Henning Kelbæk, Jens Flensted LassenLars Køber, Jacob Lønborg

Department of Cardiology

23 Citations (Scopus)

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.

Original language	English
Journal	Heart (British Cardiac Society)
Volume	104
Issue number	19
Pages (from-to)	1593-1599
Number of pages	7
ISSN	1355-6037
DOIs	https://doi.org/10.1136/heartjnl-2017-312774
Publication status	Published - Oct 2018

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Engstrøm, T., Nepper-Christensen, L., Helqvist, S., Kløvgaard, L., Holmvang, L., Jørgensen, E., Pedersen, F., Saunamaki, K., Tilsted, H.-H., Steensberg, A., Fabricius, S., Mouritzen, U., Vejlstrup, N., Ahtarovski, K. A., Göransson, C., Bertelsen, L., Kyhl, K., Olivecrona, G., Kelbæk, H., ... Lønborg, J. (2018). Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients: a phase 2 randomised clinical trial. Heart (British Cardiac Society), 104(19), 1593-1599. https://doi.org/10.1136/heartjnl-2017-312774

Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients: a phase 2 randomised clinical trial. / Engstrøm, Thomas ; Nepper-Christensen, Lars ; Helqvist, Steffen et al.
In: Heart (British Cardiac Society), Vol. 104, No. 19, 10.2018, p. 1593-1599.

Research output: Contribution to journal › Journal article › Research › peer-review

Engstrøm, T , Nepper-Christensen, L , Helqvist, S , Kløvgaard, L , Holmvang, L , Jørgensen, E , Pedersen, F, Saunamaki, K, Tilsted, H-H, Steensberg, A, Fabricius, S, Mouritzen, U, Vejlstrup, N , Ahtarovski, KA , Göransson, C , Bertelsen, L , Kyhl, K, Olivecrona, G, Kelbæk, H, Lassen, JF , Køber, L & Lønborg, J 2018, 'Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients: a phase 2 randomised clinical trial', Heart (British Cardiac Society), vol. 104, no. 19, pp. 1593-1599. https://doi.org/10.1136/heartjnl-2017-312774

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title = "Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients: a phase 2 randomised clinical trial",

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.",

author = "Thomas Engstr{\o}m and Lars Nepper-Christensen and Steffen Helqvist and Lene Kl{\o}vgaard and Lene Holmvang and Erik J{\o}rgensen and Frants Pedersen and Kari Saunamaki and Hans-Henrik Tilsted and Adam Steensberg and S{\o}ren Fabricius and Ulrik Mouritzen and Niels Vejlstrup and Ahtarovski, {Kiril A} and Christoffer G{\"o}ransson and Litten Bertelsen and Kasper Kyhl and G{\"o}ran Olivecrona and Henning Kelb{\ae}k and Lassen, {Jens Flensted} and Lars K{\o}ber and Jacob L{\o}nborg",

note = "{\textcopyright} Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.",

year = "2018",

month = oct,

doi = "10.1136/heartjnl-2017-312774",

language = "English",

volume = "104",

pages = "1593--1599",

journal = "Heart (British Cardiac Society)",

issn = "1355-6037",

publisher = "B M J Group",

number = "19",

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TY - JOUR

T1 - Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients

T2 - a phase 2 randomised clinical trial

AU - Engstrøm, Thomas

AU - Nepper-Christensen, Lars

AU - Helqvist, Steffen

AU - Kløvgaard, Lene

AU - Holmvang, Lene

AU - Jørgensen, Erik

AU - Pedersen, Frants

AU - Saunamaki, Kari

AU - Tilsted, Hans-Henrik

AU - Steensberg, Adam

AU - Fabricius, Søren

AU - Mouritzen, Ulrik

AU - Vejlstrup, Niels

AU - Ahtarovski, Kiril A

AU - Göransson, Christoffer

AU - Bertelsen, Litten

AU - Kyhl, Kasper

AU - Olivecrona, Göran

AU - Kelbæk, Henning

AU - Lassen, Jens Flensted

AU - Køber, Lars

AU - Lønborg, Jacob

PY - 2018/10

Y1 - 2018/10

N2 - 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.

AB - 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.

U2 - 10.1136/heartjnl-2017-312774

DO - 10.1136/heartjnl-2017-312774

M3 - Journal article

C2 - 29602883

SN - 1355-6037

VL - 104

SP - 1593

EP - 1599

JO - Heart (British Cardiac Society)

JF - Heart (British Cardiac Society)

IS - 19

ER -

Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients: a phase 2 randomised clinical trial

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