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A nonrandomized open-label phase 2 trial of nonischemic heart preservation for human heart transplantation

Nilsson, Johan LU ; Jernryd, Victoria LU ; Qin, Guangqi LU ; Paskevicius, Audrius LU ; Metzsch, Carsten LU ; Sjöberg, Trygve LU and Steen, Stig LU (2020) In Nature Communications 11(1).
Abstract

Pre-clinical heart transplantation studies have shown that ex vivo non-ischemic heart preservation (NIHP) can be safely used for 24 h. Here we perform a prospective, open-label, non-randomized phase II study comparing NIHP to static cold preservation (SCS), the current standard for adult heart transplantation. All adult recipients on waiting lists for heart transplantation were included in the study, unless they met any exclusion criteria. The same standard acceptance criteria for donor hearts were used in both study arms. NIHP was scheduled in advance based on availability of device and trained team members. The primary endpoint was a composite of survival free of severe primary graft dysfunction, free of ECMO use within 7 days, and... (More)

Pre-clinical heart transplantation studies have shown that ex vivo non-ischemic heart preservation (NIHP) can be safely used for 24 h. Here we perform a prospective, open-label, non-randomized phase II study comparing NIHP to static cold preservation (SCS), the current standard for adult heart transplantation. All adult recipients on waiting lists for heart transplantation were included in the study, unless they met any exclusion criteria. The same standard acceptance criteria for donor hearts were used in both study arms. NIHP was scheduled in advance based on availability of device and trained team members. The primary endpoint was a composite of survival free of severe primary graft dysfunction, free of ECMO use within 7 days, and free of acute cellular rejection ≥2R within 180 days. Secondary endpoints were I/R-tissue injury, immediate graft function, and adverse events. Of the 31 eligible patients, six were assigned to NIHP and 25 to SCS. The median preservation time was 223 min (IQR, 202–263) for NIHP and 194 min (IQR, 164–223) for SCS. Over the first six months, all of the patients assigned to NIHP achieved event-free survival, compared with 18 of those assigned to SCS (Kaplan-Meier estimate of event free survival 72.0% [95% CI 50.0–86.0%]). CK-MB assessed 6 ± 2 h after ending perfusion was 76 (IQR, 50–101) ng/mL for NIHP compared with 138 (IQR, 72–198) ng/mL for SCS. Four deaths within six months after transplantation and three cardiac-related adverse events were reported in the SCS group compared with no deaths or cardiac-related adverse events in the NIHP group. This first-in-human study shows the feasibility and safety of NIHP for clinical use in heart transplantation. ClinicalTrial.gov, number NCT03150147.

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publication status
published
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in
Nature Communications
volume
11
issue
1
article number
2976
publisher
Nature Publishing Group
external identifiers
  • pmid:32532991
  • scopus:85086394749
ISSN
2041-1723
DOI
10.1038/s41467-020-16782-9
language
English
LU publication?
yes
id
8d3a8b79-48a1-4b25-b2c5-2a1e35f15845
date added to LUP
2020-06-26 08:39:27
date last changed
2020-07-01 05:34:26
@article{8d3a8b79-48a1-4b25-b2c5-2a1e35f15845,
  abstract     = {<p>Pre-clinical heart transplantation studies have shown that ex vivo non-ischemic heart preservation (NIHP) can be safely used for 24 h. Here we perform a prospective, open-label, non-randomized phase II study comparing NIHP to static cold preservation (SCS), the current standard for adult heart transplantation. All adult recipients on waiting lists for heart transplantation were included in the study, unless they met any exclusion criteria. The same standard acceptance criteria for donor hearts were used in both study arms. NIHP was scheduled in advance based on availability of device and trained team members. The primary endpoint was a composite of survival free of severe primary graft dysfunction, free of ECMO use within 7 days, and free of acute cellular rejection ≥2R within 180 days. Secondary endpoints were I/R-tissue injury, immediate graft function, and adverse events. Of the 31 eligible patients, six were assigned to NIHP and 25 to SCS. The median preservation time was 223 min (IQR, 202–263) for NIHP and 194 min (IQR, 164–223) for SCS. Over the first six months, all of the patients assigned to NIHP achieved event-free survival, compared with 18 of those assigned to SCS (Kaplan-Meier estimate of event free survival 72.0% [95% CI 50.0–86.0%]). CK-MB assessed 6 ± 2 h after ending perfusion was 76 (IQR, 50–101) ng/mL for NIHP compared with 138 (IQR, 72–198) ng/mL for SCS. Four deaths within six months after transplantation and three cardiac-related adverse events were reported in the SCS group compared with no deaths or cardiac-related adverse events in the NIHP group. This first-in-human study shows the feasibility and safety of NIHP for clinical use in heart transplantation. ClinicalTrial.gov, number NCT03150147.</p>},
  author       = {Nilsson, Johan and Jernryd, Victoria and Qin, Guangqi and Paskevicius, Audrius and Metzsch, Carsten and Sjöberg, Trygve and Steen, Stig},
  issn         = {2041-1723},
  language     = {eng},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {A nonrandomized open-label phase 2 trial of nonischemic heart preservation for human heart transplantation},
  url          = {http://dx.doi.org/10.1038/s41467-020-16782-9},
  doi          = {10.1038/s41467-020-16782-9},
  volume       = {11},
  year         = {2020},
}