Jens Gottlieb1,2, Alexander Reuss3, Konstantin Mayer4, Karin Weide3, Carmen Schade-Brittinger3, Susanne Hoyer5,6, Peter Jaksch7. 1. Department of Respiratory Medicine OE6870, Hannover Medical School, 30625, Hannover, Germany. gottlieb.jens@mh-hannover.de. 2. BREATH (Biomedical Research in End-stage and obstructive Lung Disease Hannover), Hannover, Germany. gottlieb.jens@mh-hannover.de. 3. Coordinating Centre for Clinical Trials Marburg (KKS Marburg), Philipps-University Marburg, Marburg, Germany. 4. University of Giessen and Marburg Lung Center (UGMLC), University Hospital Giessen, Justus Liebig University of Giessen, Giessen, Germany. 5. Department of Respiratory Medicine OE6870, Hannover Medical School, 30625, Hannover, Germany. 6. BREATH (Biomedical Research in End-stage and obstructive Lung Disease Hannover), Hannover, Germany. 7. Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
Abstract
BACKGROUND: Immunosuppression including high-dose calcineurin inhibitors (CNI) is essential after lung transplantation. Dosing is usually guided by therapeutic drug monitoring adjusted to target trough levels of CNIs to keep the balance between over-dose causing severe toxicity and increased risk of infections or under-dose with a risk of graft injury. Adaptation of CNI-based immunosuppression by monitoring of torque teno virus (TTV), a latent nonpathogenic DNA virus, measured in the whole blood in addition to conventional therapeutic drug monitoring may reduce the toxicity of immunosuppression with similar efficacy. METHODS/ DESIGN: An open-label, randomized, controlled, parallel-group, multicenter trial in lung transplant recipients will be conducted to investigate the safety and efficacy of immunosuppression guided by TTV monitoring as an add-on to conventional therapeutic drug monitoring. Adult lung transplant recipients 21 to 42 days after transplantation are eligible to participate. Patients (N = 144) will be randomized 1:1 to the experimental intervention (arm 1: immunosuppression guided by TTV monitoring in addition to conventional therapeutic drug monitoring of tacrolimus trough levels) and control intervention (arm 2: conventional therapeutic drug monitoring). Outcomes will be assessed 12 months after randomization with the change in glomerular filtration rate as the primary endpoint. Secondary endpoints will be additional measurements of renal function, allograft function, incidence of acute rejections, incidence of chronic lung allograft dysfunction, graft loss, and infections. DISCUSSION: The results of this randomized controlled trial may reduce the toxicity of immunosuppression after lung transplantation while maintaining the efficacy of immunosuppression. Study results are transferable to all other solid organ transplantations. TRIAL REGISTRATION: ClinicalTrials.gov NCT04198506 . Registered on 12 December 2019.
RCT Entities:
BACKGROUND: Immunosuppression including high-dose calcineurin inhibitors (CNI) is essential after lung transplantation. Dosing is usually guided by therapeutic drug monitoring adjusted to target trough levels of CNIs to keep the balance between over-dose causing severe toxicity and increased risk of infections or under-dose with a risk of graft injury. Adaptation of CNI-based immunosuppression by monitoring of torque teno virus (TTV), a latent nonpathogenic DNA virus, measured in the whole blood in addition to conventional therapeutic drug monitoring may reduce the toxicity of immunosuppression with similar efficacy. METHODS/ DESIGN: An open-label, randomized, controlled, parallel-group, multicenter trial in lung transplant recipients will be conducted to investigate the safety and efficacy of immunosuppression guided by TTV monitoring as an add-on to conventional therapeutic drug monitoring. Adult lung transplant recipients 21 to 42 days after transplantation are eligible to participate. Patients (N = 144) will be randomized 1:1 to the experimental intervention (arm 1: immunosuppression guided by TTV monitoring in addition to conventional therapeutic drug monitoring of tacrolimus trough levels) and control intervention (arm 2: conventional therapeutic drug monitoring). Outcomes will be assessed 12 months after randomization with the change in glomerular filtration rate as the primary endpoint. Secondary endpoints will be additional measurements of renal function, allograft function, incidence of acute rejections, incidence of chronic lung allograft dysfunction, graft loss, and infections. DISCUSSION: The results of this randomized controlled trial may reduce the toxicity of immunosuppression after lung transplantation while maintaining the efficacy of immunosuppression. Study results are transferable to all other solid organ transplantations. TRIAL REGISTRATION: ClinicalTrials.gov NCT04198506 . Registered on 12 December 2019.
Authors: Peter Jaksch; Michael Kundi; Irene Görzer; Gabriella Muraközy; Christopher Lambers; Alberto Benazzo; Konrad Hoetzenecker; Walter Klepetko; Elisabeth Puchhammer-Stöckl Journal: J Infect Dis Date: 2018-11-05 Impact factor: 5.226
Authors: Anne E Holland; Martijn A Spruit; Thierry Troosters; Milo A Puhan; Véronique Pepin; Didier Saey; Meredith C McCormack; Brian W Carlin; Frank C Sciurba; Fabio Pitta; Jack Wanger; Neil MacIntyre; David A Kaminsky; Bruce H Culver; Susan M Revill; Nidia A Hernandes; Vasileios Andrianopoulos; Carlos Augusto Camillo; Katy E Mitchell; Annemarie L Lee; Catherine J Hill; Sally J Singh Journal: Eur Respir J Date: 2014-10-30 Impact factor: 16.671
Authors: Ramsey R Hachem; Roger D Yusen; Murali M Chakinala; Bryan F Meyers; John P Lynch; Aviva A Aloush; G Alexander Patterson; Elbert P Trulock Journal: J Heart Lung Transplant Date: 2007-10 Impact factor: 10.247
Authors: Andrew S Levey; Lesley A Stevens; Christopher H Schmid; Yaping Lucy Zhang; Alejandro F Castro; Harold I Feldman; John W Kusek; Paul Eggers; Frederick Van Lente; Tom Greene; Josef Coresh Journal: Ann Intern Med Date: 2009-05-05 Impact factor: 25.391
Authors: Irene Görzer; Peter Jaksch; Michael Kundi; Tamara Seitz; Walter Klepetko; Elisabeth Puchhammer-Stöckl Journal: PLoS One Date: 2015-04-20 Impact factor: 3.240
Authors: Iwijn De Vlaminck; Kiran K Khush; Calvin Strehl; Bitika Kohli; Helen Luikart; Norma F Neff; Jennifer Okamoto; Thomas M Snyder; David N Cornfield; Mark R Nicolls; David Weill; Daniel Bernstein; Hannah A Valantine; Stephen R Quake Journal: Cell Date: 2013-11-21 Impact factor: 41.582