Short-course, direct-acting antivirals and ezetimibe to prevent HCV infection in recipients of organs from HCV-infected donors: a phase 3, single-centre, open-label study.
Adult
Aged
Anticholesteremic Agents
/ administration & dosage
Antiviral Agents
/ administration & dosage
Benzimidazoles
/ administration & dosage
Canada
/ epidemiology
Drug Administration Schedule
Drug Combinations
Drug Therapy, Combination
Ezetimibe
/ administration & dosage
Female
Genotype
Hepacivirus
/ genetics
Hepatitis C, Chronic
/ drug therapy
Humans
Male
Middle Aged
Pyrrolidines
/ administration & dosage
Quinoxalines
/ administration & dosage
RNA Viruses
/ genetics
Sulfonamides
/ administration & dosage
Tissue Donors
/ statistics & numerical data
Transplant Recipients
/ statistics & numerical data
Transplants
/ virology
Viral Load
/ statistics & numerical data
Journal
The lancet. Gastroenterology & hepatology
ISSN: 2468-1253
Titre abrégé: Lancet Gastroenterol Hepatol
Pays: Netherlands
ID NLM: 101690683
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
13
01
2020
revised:
28
02
2020
accepted:
12
03
2020
pubmed:
12
5
2020
medline:
28
8
2020
entrez:
12
5
2020
Statut:
ppublish
Résumé
An increasing percentage of potential organ donors are infected with hepatitis C virus (HCV). After transplantation from an infected donor, establishment of HCV infection in uninfected recipients is near-universal, with the requirement for post-transplant antiviral treatment. The aim of this study was to determine if antiviral drugs combined with an HCV entry blocker given before and for 7 days after transplant would be safe and reduce the likelihood of HCV infection in recipients of organs from HCV-infected donors. HCV-uninfected organ recipients without pre-existing liver disease were treated with ezetimibe (10 mg; an HCV entry inhibitor) and glecaprevir-pibrentasvir (300 mg/120 mg) before and after transplantation from HCV-infected donors aged younger than 70 years without co-infection with HIV, hepatitis B virus, or human T-cell leukaemia virus 1 or 2. Recipients received a single dose 6-12 h before transplant and once a day for 7 days after surgery (eight doses in total). HCV RNA was assessed once a day for 14 days and then once a week until 12 weeks post-transplant. The primary endpoint was prevention of chronic HCV infection, as evidenced by undetectable serum HCV RNA at 12 weeks after transplant, and assessed in the intention-to-treat population. Safety monitoring was according to routine post-transplant practice. 12-week data are reported for the first 30 patients. The trial is registered on ClinicalTrials.gov, NCT04017338. The trial is closed to recruitment but follow-up is ongoing. 30 patients (23 men and seven women; median age 61 years (IQR 48-66) received transplants (13 lung, ten kidney, six heart, and one kidney-pancreas) from 18 HCV-infected donors. The median donor viral load was 5·11 log Ezetimibe combined with glecaprevir-pibrentasvir given one dose before and for 7 days after transplant prevented the establishment of chronic HCV infection in recipients of different organs from HCV-infected donors. This study shows that an ultra-short course of direct-acting antivirals and ezetimibe can prevent the establishment of chronic HCV infection in the recipient, alleviating many of the concerns with transplanting organs from HCV-infected donors. Canadian Institutes of Health Research; the Organ Transplant Program, University Health Network.
Sections du résumé
BACKGROUND
An increasing percentage of potential organ donors are infected with hepatitis C virus (HCV). After transplantation from an infected donor, establishment of HCV infection in uninfected recipients is near-universal, with the requirement for post-transplant antiviral treatment. The aim of this study was to determine if antiviral drugs combined with an HCV entry blocker given before and for 7 days after transplant would be safe and reduce the likelihood of HCV infection in recipients of organs from HCV-infected donors.
METHODS
HCV-uninfected organ recipients without pre-existing liver disease were treated with ezetimibe (10 mg; an HCV entry inhibitor) and glecaprevir-pibrentasvir (300 mg/120 mg) before and after transplantation from HCV-infected donors aged younger than 70 years without co-infection with HIV, hepatitis B virus, or human T-cell leukaemia virus 1 or 2. Recipients received a single dose 6-12 h before transplant and once a day for 7 days after surgery (eight doses in total). HCV RNA was assessed once a day for 14 days and then once a week until 12 weeks post-transplant. The primary endpoint was prevention of chronic HCV infection, as evidenced by undetectable serum HCV RNA at 12 weeks after transplant, and assessed in the intention-to-treat population. Safety monitoring was according to routine post-transplant practice. 12-week data are reported for the first 30 patients. The trial is registered on ClinicalTrials.gov, NCT04017338. The trial is closed to recruitment but follow-up is ongoing.
FINDINGS
30 patients (23 men and seven women; median age 61 years (IQR 48-66) received transplants (13 lung, ten kidney, six heart, and one kidney-pancreas) from 18 HCV-infected donors. The median donor viral load was 5·11 log
INTERPRETATION
Ezetimibe combined with glecaprevir-pibrentasvir given one dose before and for 7 days after transplant prevented the establishment of chronic HCV infection in recipients of different organs from HCV-infected donors. This study shows that an ultra-short course of direct-acting antivirals and ezetimibe can prevent the establishment of chronic HCV infection in the recipient, alleviating many of the concerns with transplanting organs from HCV-infected donors.
FUNDING
Canadian Institutes of Health Research; the Organ Transplant Program, University Health Network.
Identifiants
pubmed: 32389183
pii: S2468-1253(20)30081-9
doi: 10.1016/S2468-1253(20)30081-9
pmc: PMC7391837
mid: NIHMS1603473
pii:
doi:
Substances chimiques
Anticholesteremic Agents
0
Antiviral Agents
0
Benzimidazoles
0
Drug Combinations
0
Pyrrolidines
0
Quinoxalines
0
Sulfonamides
0
glecaprevir and pibrentasvir
0
Ezetimibe
EOR26LQQ24
Banques de données
ClinicalTrials.gov
['NCT04017338']
Types de publication
Clinical Trial, Phase III
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
649-657Subventions
Organisme : NIAID NIH HHS
ID : U01 AI063594–11
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI078881
Pays : United States
Organisme : NCHHSTP CDC HHS
ID : U51 PS004607
Pays : United States
Organisme : CSRD VA
ID : I01 CX001398
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM121600
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
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