Research
Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial
1 Hospices Civils de Lyon, Hôpital Louis Pradel, Pôle Médico-Chirurgical de Transplantation Cardiaque Adulte, 28, avenue du Doyen Lépine, F-69677, Bron Cedex, France
2 INSERM, CIC 201, Lyon, Hospices Civils de Lyon, Service de Pharmacologie Clinique et Essais Thérapeutiques, Université Lyon 1, 7 Rue Guillaume Paradin, F-69000, Lyon, France
3 Hospices Civils de Lyon, Service de Biostatistique, 162, avenue Lacassagne, F-69003, Lyon, France
4 Département de Chirurgie Cardiaque, Hôpital Charles Nicolle, Université de Rouen, 1, rue de Germont, F-76000, Rouen, France
5 Service de Cardiologie, Centre Hospitalier et Universitaire de Rennes, 2 rue Henri le Guilloux, F-35033, Rennes, France
6 Département de Cardiologie et Transplantation, Hôpital Brabois, rue du Morvan, F-54511, Nancy, France
7 Service de Chirurgie Cardiaque Adultes, Hôpital Timone, 264 rue Saint-Pierre, F-13385, Marseille, France
8 Département de Cardiologie et Transplantation, Hôpital Guillaume et René Laënnec, boulevard Jacques Monod, F-44093, Nantes, France
9 Service de Chirurgie Cardiaque, Centre Hospitalier Universitaire de Tours, 41, boulevard Béranger, F-37044, Tours, France
10 Service de Chirurgie Cardiaque, Les Hôpitaux Universitaires de Strasbourg, 3, rue Koeberlé, F-67000, Strasbourg, France
11 Département de Chirurgie Thoracique et Cardiovasculaire, Groupe Hospitalier la Pitié-Salpêtrière, 47-83 boulevard de l'hôpital, F-75013, Paris, France
12 Département de Cardiologie et Transplantation, Centre Hospitalier du Haut Levèque, avenue de Magellan, 33604, Pessac, France
13 CNRS and Université Lyon 1, UMR5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biotatistique-Santé, 162, avenue Lacassagne, F-69003, Lyon, France
14 CNRS and Université Lyon 1, UMR5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Modélisation et Evaluation des Thérapeutiques, 7 Rue Guillaume Paradin, F-69000, Lyon, France
Trials 2012, 13:231 doi:10.1186/1745-6215-13-231
Published: 3 December 2012Abstract
Background
Using reduced doses of Cyclosporine A immediately after heart transplantation in clinical trials may suggest benefits for renal function by reducing serum creatinine levels without a significant change in clinical endpoints. However, these trials were not sufficiently powered to prove clinical outcomes.
Methods
In a prospective, multicentre, open-label, parallel-group controlled trial, 95 patients aged 18 to 65 years old, undergoing de novo heart transplantation were centrally randomised to receive either a low (130 < trough CsA concentrations <200 μg/L, n = 47) or a standard dose of Cyclosporine A (200 < trough CsA concentrations <300 μg/L, n = 48) for the three first post-transplant months along with mycophenolate mofetil and corticosteroids. Participants had a stable haemodynamic status, a serum creatinine level <250 μmol/L and the donors’ cold ischemia time was under six hours; multiorgan transplants were excluded. The change in serum creatinine level over 12 months was used as the main criterion for renal function. Intention-to-treat analysis was performed on the 95 randomised patients and a mixed generalised linear model of covariance was applied.
Results
At 12 months, the mean (± SD) creatinine value was 120.7 μmol/L (± 35.8) in the low-dose group and 132.3 μmol/L (± 49.1) in the standard-dose group (P = 0.162). Post hoc analyses suggested that patients with higher creatinine levels at baseline benefited significantly from the lower Cyclosporine A target. The number of patients with at least one rejection episode was not significantly different but one patient in the low-dose group and six in the standard-dose group required dialysis.
Conclusions
In patients with de novo cardiac transplantation, early Cyclosporine A dose reduction was not associated with renal benefit at 12 months. However, the strategy may benefit patients with high creatinine levels before transplantation.
Trial registration
ClinicalTrials.gov NCT00159159
