Pre-emptive pangenotypic direct acting antiviral therapy in donor HCV-positive to recipient HCV-negative heart transplantation: an open-label study.

Adult Aged Antiviral Agents / therapeutic use Benzimidazoles / therapeutic use Drug Combinations Female Follow-Up Studies Heart / virology Heart Transplantation Hemodynamics Hepacivirus / isolation & purification Hepatitis C, Chronic / prevention & control Humans Male Middle Aged Proof of Concept Study Pyrrolidines / therapeutic use Quinoxalines / therapeutic use Sulfonamides / therapeutic use Tissue Donors Waiting Lists Young Adult

Journal

The lancet. Gastroenterology & hepatology

ISSN: 2468-1253

Titre abrégé: Lancet Gastroenterol Hepatol

Pays: Netherlands

ID NLM: 101690683

Informations de publication

Date de publication:
10 2019

Historique:

received: 12 05 2019

revised: 06 06 2019

accepted: 17 06 2019

pubmed: 30 7 2019

medline: 22 5 2020

entrez: 30 7 2019

Statut: ppublish

Résumé

Low donor heart availability underscores the need to identify all potentially transplantable organs. We sought to determine whether pre-emptive administration of pangenotypic direct-acting antiviral therapy can safely prevent the development of chronic hepatitis C virus (HCV) infection in uninfected recipients of HCV-infected donor hearts. Patients were recruited for this an open-label, single-centre, proof-of-concept study from Nov 1, 2017, to Nov 30, 2018. Following enrolment, the recipient's status on the heart transplantation waiting list was updated to reflect a willingness to accept either an HCV-positive or HCV-negative heart donor. Patients who underwent transplantation with a viraemic donor heart, as determined by nucleic acid testing (NAT), received pre-emptive oral glecaprevir-pibrentasvir before transport to the operating room followed by an 8-week course of glecaprevir-pibrentasvir after transplantation. Patients receiving HCV antibody-positive donor hearts without detectable circulating HCV RNA were followed using a reactive approach and started glecaprevir-pibrentasvir only if they developed viraemia. The primary outcome was achievement of sustained virological response 12 weeks after completion of glecaprevir-pibrentasvir therapy (SVR12). Patients were followed from study enrolment to 1 year after transplantation. This is an interim analysis, initiated after all enrolled patients reached the primary outcome. Results reflect data from Nov 1, 2017, to May 30, 2019. This trial is registered with ClinicalTrials.gov, number NCT03208244. 55 patients were assessed for eligibility and 52 consented to enrolment. 25 patients underwent heart transplantation with HCV-positive donor hearts (20 NAT-positive, five NAT-negative), three of whom underwent simultaneous heart-kidney transplantation. All 20 recipients of NAT-positive hearts tolerated glecaprevir-pibrentasvir and showed rapid viral suppression (median time to clearance 3·5 days, IQR 0·0-8·3), with the subsequent achievement of SVR12 by all 20. The five recipients of NAT-negative grafts did not become viraemic. Median pre-transplant waiting time for patients following enrolment in the HCV protocol was 20 days (IQR 8-57). Patient and allograft survival were 100% at a median follow-up of 10·7 months (range 6·5-18·0). Pre-emptive administration of glecaprevir-pibrentasvir therapy results in expedited organ transplantation, rapid HCV suppression, prevention of chronic HCV infection, and excellent early allograft function in patients receiving HCV-infected donor hearts. Long-term outcomes are not yet known. American Association for the Study of Liver Diseases, National Institutes of Health, and the Massachusetts General Hospital.

Sections du résumé

BACKGROUND

METHODS

Patients were recruited for this an open-label, single-centre, proof-of-concept study from Nov 1, 2017, to Nov 30, 2018. Following enrolment, the recipient's status on the heart transplantation waiting list was updated to reflect a willingness to accept either an HCV-positive or HCV-negative heart donor. Patients who underwent transplantation with a viraemic donor heart, as determined by nucleic acid testing (NAT), received pre-emptive oral glecaprevir-pibrentasvir before transport to the operating room followed by an 8-week course of glecaprevir-pibrentasvir after transplantation. Patients receiving HCV antibody-positive donor hearts without detectable circulating HCV RNA were followed using a reactive approach and started glecaprevir-pibrentasvir only if they developed viraemia. The primary outcome was achievement of sustained virological response 12 weeks after completion of glecaprevir-pibrentasvir therapy (SVR12). Patients were followed from study enrolment to 1 year after transplantation. This is an interim analysis, initiated after all enrolled patients reached the primary outcome. Results reflect data from Nov 1, 2017, to May 30, 2019. This trial is registered with ClinicalTrials.gov, number NCT03208244.

FINDINGS

55 patients were assessed for eligibility and 52 consented to enrolment. 25 patients underwent heart transplantation with HCV-positive donor hearts (20 NAT-positive, five NAT-negative), three of whom underwent simultaneous heart-kidney transplantation. All 20 recipients of NAT-positive hearts tolerated glecaprevir-pibrentasvir and showed rapid viral suppression (median time to clearance 3·5 days, IQR 0·0-8·3), with the subsequent achievement of SVR12 by all 20. The five recipients of NAT-negative grafts did not become viraemic. Median pre-transplant waiting time for patients following enrolment in the HCV protocol was 20 days (IQR 8-57). Patient and allograft survival were 100% at a median follow-up of 10·7 months (range 6·5-18·0).

INTERPRETATION

Pre-emptive administration of glecaprevir-pibrentasvir therapy results in expedited organ transplantation, rapid HCV suppression, prevention of chronic HCV infection, and excellent early allograft function in patients receiving HCV-infected donor hearts. Long-term outcomes are not yet known.

FUNDING

American Association for the Study of Liver Diseases, National Institutes of Health, and the Massachusetts General Hospital.

Identifiants

DOI: 10.1016/S2468-1253(19)30240-7 PMID: 31353243

pubmed: 31353243

pii: S2468-1253(19)30240-7

doi: 10.1016/S2468-1253(19)30240-7

pii:

doi:

Substances chimiques

Antiviral Agents 0

Benzimidazoles 0

Drug Combinations 0

Pyrrolidines 0

Quinoxalines 0

Sulfonamides 0

glecaprevir and pibrentasvir 0

Banques de données

ClinicalTrials.gov

['NCT03208244']

Types de publication

Clinical Trial Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

771-780

Commentaires et corrections

Type : CommentIn