Intravenously administered interleukin-7 to reverse lymphopenia in patients with septic shock: a double-blind, randomized, placebo-controlled trial.
Immune restoration
Interleukin-7
Lymphocyte
Sepsis
Journal
Annals of intensive care
ISSN: 2110-5820
Titre abrégé: Ann Intensive Care
Pays: Germany
ID NLM: 101562873
Informations de publication
Date de publication:
12 Mar 2023
12 Mar 2023
Historique:
received:
10
10
2022
accepted:
07
02
2023
entrez:
12
3
2023
pubmed:
13
3
2023
medline:
13
3
2023
Statut:
epublish
Résumé
Profound lymphopenia is an independent predictor of adverse clinical outcomes in sepsis. Interleukin-7 (IL-7) is essential for lymphocyte proliferation and survival. A previous phase II study showed that CYT107, a glycosylated recombinant human IL-7, administered intramuscularly reversed sepsis-induced lymphopenia and improved lymphocyte function. Thepresent study evaluated intravenous administration of CYT107. This prospective, double-blinded, placebo-controlled trial was designed to enroll 40 sepsis patients, randomized 3:1 to CYT107 (10 µg/kg) or placebo, for up to 90 days. Twenty-one patients were enrolled (fifteen CYT107 group, six placebo group) at eight French and two US sites. The study was halted early because three of fifteen patients receiving intravenous CYT107 developed fever and respiratory distress approximately 5-8 h after drug administration. Intravenous administration of CYT107 resulted in a two-threefold increase in absolute lymphocyte counts (including in both CD4 Intravenous CYT107 reversed sepsis-induced lymphopenia. However, compared to intramuscular CYT107 administration, it was associated with transient respiratory distress without long-term sequelae. Because of equivalent positive laboratory and clinical responses, more favorable pharmacokinetics, and better patient tolerability, intramuscular administration of CYT107 is preferable. Clinicaltrials.gov, NCT03821038. Registered 29 January 2019, https://clinicaltrials.gov/ct2/show/NCT03821038?term=NCT03821038&draw=2&rank=1 .
Sections du résumé
BACKGROUND
BACKGROUND
Profound lymphopenia is an independent predictor of adverse clinical outcomes in sepsis. Interleukin-7 (IL-7) is essential for lymphocyte proliferation and survival. A previous phase II study showed that CYT107, a glycosylated recombinant human IL-7, administered intramuscularly reversed sepsis-induced lymphopenia and improved lymphocyte function. Thepresent study evaluated intravenous administration of CYT107. This prospective, double-blinded, placebo-controlled trial was designed to enroll 40 sepsis patients, randomized 3:1 to CYT107 (10 µg/kg) or placebo, for up to 90 days.
RESULTS
RESULTS
Twenty-one patients were enrolled (fifteen CYT107 group, six placebo group) at eight French and two US sites. The study was halted early because three of fifteen patients receiving intravenous CYT107 developed fever and respiratory distress approximately 5-8 h after drug administration. Intravenous administration of CYT107 resulted in a two-threefold increase in absolute lymphocyte counts (including in both CD4
CONCLUSION
CONCLUSIONS
Intravenous CYT107 reversed sepsis-induced lymphopenia. However, compared to intramuscular CYT107 administration, it was associated with transient respiratory distress without long-term sequelae. Because of equivalent positive laboratory and clinical responses, more favorable pharmacokinetics, and better patient tolerability, intramuscular administration of CYT107 is preferable.
TRIAL REGISTRATION
BACKGROUND
Clinicaltrials.gov, NCT03821038. Registered 29 January 2019, https://clinicaltrials.gov/ct2/show/NCT03821038?term=NCT03821038&draw=2&rank=1 .
Identifiants
pubmed: 36906875
doi: 10.1186/s13613-023-01109-w
pii: 10.1186/s13613-023-01109-w
pmc: PMC10008152
doi:
Banques de données
ClinicalTrials.gov
['NCT03821038']
Types de publication
Journal Article
Langues
eng
Pagination
17Informations de copyright
© 2023. The Author(s).
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