Three-year results of an investigator-driven multicenter, international, randomized open-label de novo trial to prevent BOS after lung transplantation
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Three-year results of an investigator-driven multicenter, international, randomized open-label de novo trial to prevent BOS after lung transplantation. / Glanville, Allan R; Aboyoun, Christina; Klepetko, Walter; Reichenspurner, Hermann; Treede, Hendrik; Verschuuren, Erik A; Boehler, Annette; Benden, Christian; Hopkins, Peter; Corris, Paul A; European and Australian Investigators in Lung Transplantation.
in: J HEART LUNG TRANSPL, Jahrgang 34, Nr. 1, 01.2015, S. 16-25.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Three-year results of an investigator-driven multicenter, international, randomized open-label de novo trial to prevent BOS after lung transplantation
AU - Glanville, Allan R
AU - Aboyoun, Christina
AU - Klepetko, Walter
AU - Reichenspurner, Hermann
AU - Treede, Hendrik
AU - Verschuuren, Erik A
AU - Boehler, Annette
AU - Benden, Christian
AU - Hopkins, Peter
AU - Corris, Paul A
AU - European and Australian Investigators in Lung Transplantation
N1 - Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
PY - 2015/1
Y1 - 2015/1
N2 - BACKGROUND: Chronic lung allograft dysfunction (CLAD), predominantly manifest as bronchiolitis obliterans syndrome (BOS), is the primary cause of morbidity and death after lung transplantation. We assessed the efficacy and safety of 2 de novo immunosuppression protocols to prevent BOS.METHODS: This was a multicenter, prospective, international, randomized (1:1) open-label superiority study of de novo enteric-coated mycophenolate sodium (MPS) vs delayed-onset everolimus (RAD), both arms in combination with cyclosporine (CsA) monitored by 2-hour post-dose (C2) levels, and corticosteroids. Target C2 levels were lower in the RAD group because RAD is known to potentiate CsA nephrotoxicity. Cytolytic induction therapy was not used. Patients were stratified at entry for cystic fibrosis. Confirmation of anastomotic healing was required for randomization. Primary efficacy was freedom from BOS Grade 1 on intention-to-treat (ITT) analysis. Secondary efficacy parameters were patient and graft survival and severity of rejection. Treatment failure was defined by graft loss, patient death, drug cessation, or need for other therapy.RESULTS: The 3-year freedom from BOS Grade 1 was 70% for MPS (n = 80) vs 71% for RAD (n = 84; p = 0.95 by log-rank) in ITT but was lower in the RAD arm of the per-protocol population (p = 0.03). The 3-year survival was 84% (MPS) vs 76% (RAD; p = 0.19 by log-rank). Thirteen patients switched from MPS vs 31 from RAD (p < 0.01). Days on MPS were greater than days on RAD (p < 0.01). Rejection events proven by biopsy specimen were more common on MPS (p = 0.02), as were leucopenia (p < 0.01), diarrhea (p < 0.01), and cytomegalovirus infection (p = 0.04). Venous thromboembolism was more frequent on RAD (p = 0.02). Creatinine at 3 years was 160 ± 112 μmol/1iter in MPS patients vs 152 ± 98 μmol/1iter in RAD patients (p = 0.67).CONCLUSIONS: This 3-year ITT analysis found no significant difference between arms but was underpowered to accept the null hypothesis that RAD and MPS have equivalent efficacy in preventing BOS or death after lung transplantation.
AB - BACKGROUND: Chronic lung allograft dysfunction (CLAD), predominantly manifest as bronchiolitis obliterans syndrome (BOS), is the primary cause of morbidity and death after lung transplantation. We assessed the efficacy and safety of 2 de novo immunosuppression protocols to prevent BOS.METHODS: This was a multicenter, prospective, international, randomized (1:1) open-label superiority study of de novo enteric-coated mycophenolate sodium (MPS) vs delayed-onset everolimus (RAD), both arms in combination with cyclosporine (CsA) monitored by 2-hour post-dose (C2) levels, and corticosteroids. Target C2 levels were lower in the RAD group because RAD is known to potentiate CsA nephrotoxicity. Cytolytic induction therapy was not used. Patients were stratified at entry for cystic fibrosis. Confirmation of anastomotic healing was required for randomization. Primary efficacy was freedom from BOS Grade 1 on intention-to-treat (ITT) analysis. Secondary efficacy parameters were patient and graft survival and severity of rejection. Treatment failure was defined by graft loss, patient death, drug cessation, or need for other therapy.RESULTS: The 3-year freedom from BOS Grade 1 was 70% for MPS (n = 80) vs 71% for RAD (n = 84; p = 0.95 by log-rank) in ITT but was lower in the RAD arm of the per-protocol population (p = 0.03). The 3-year survival was 84% (MPS) vs 76% (RAD; p = 0.19 by log-rank). Thirteen patients switched from MPS vs 31 from RAD (p < 0.01). Days on MPS were greater than days on RAD (p < 0.01). Rejection events proven by biopsy specimen were more common on MPS (p = 0.02), as were leucopenia (p < 0.01), diarrhea (p < 0.01), and cytomegalovirus infection (p = 0.04). Venous thromboembolism was more frequent on RAD (p = 0.02). Creatinine at 3 years was 160 ± 112 μmol/1iter in MPS patients vs 152 ± 98 μmol/1iter in RAD patients (p = 0.67).CONCLUSIONS: This 3-year ITT analysis found no significant difference between arms but was underpowered to accept the null hypothesis that RAD and MPS have equivalent efficacy in preventing BOS or death after lung transplantation.
KW - Adult
KW - Aged
KW - Anti-Inflammatory Agents, Non-Steroidal
KW - Antineoplastic Agents
KW - Bronchiolitis Obliterans/etiology
KW - Drug Therapy, Combination
KW - Everolimus
KW - Female
KW - Follow-Up Studies
KW - Graft Survival
KW - Humans
KW - Immunosuppressive Agents/administration & dosage
KW - Lung Transplantation/adverse effects
KW - Male
KW - Middle Aged
KW - Mycophenolic Acid/administration & dosage
KW - Postoperative Complications/etiology
KW - Prospective Studies
KW - Sirolimus/administration & dosage
KW - Time Factors
KW - Treatment Outcome
KW - Young Adult
U2 - 10.1016/j.healun.2014.06.001
DO - 10.1016/j.healun.2014.06.001
M3 - SCORING: Journal article
C2 - 25049068
VL - 34
SP - 16
EP - 25
JO - J HEART LUNG TRANSPL
JF - J HEART LUNG TRANSPL
SN - 1053-2498
IS - 1
ER -