Clinical trial NCT02284464: Steroid Withdrawal and Donor-specific Anti-HLA Antibodies in Renal Transplant Patients
Official title: Steroid Withdrawal and Novo Donor-specific Anti-HLA Antibodies in Renal Transplant Patients: a Prospective, Randomized and Controlled Study in Parallel Groups
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Other Complication of Kidney Transplant
Renal Transplant Rejection
Keywords: Kidney transplant
Immunosuppression
Steroid withdrawal
Donor specific antibodies
Lead sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
Sponsor class: OTHER
Collaborators: name: Sociedad Andaluza de Trasplantes de Organos y Tejidos
First posted: 2014-11-06
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Steroids are one of the pillars of immunosuppression for kidney transplant patients but their use is associated with a high rate of complications. Withdrawal of steroids reduces some metabolic and cardiovascular complications, but it may increase the risk of acute rejection. However, little is known about whether steroid withdrawal is associated with the generation of anti-HLA donor-specific antibodies (DSA) and the relation between DSA and clinical and histological data. The aim of this study is to compare the incidence of de novo anti-HLA DSA in stable kidney transplant patients after withdrawing the steroids 3 months after the transplantation as compared with patients who continue with steroids. The hypothesis is that steroid withdrawal will increase the presence of de novo anti-HLA DSA in stable kidney transplant patients


Eligibility criteria: Inclusion Criteria:

1. Male and female patients aged over 18 years with no immunological risk (PRA \<25% and no DSA) who are receiving their first cadaveric or living kidney transplant.
2. Patients who, three months after the transplantation, are receiving tacrolimus in combination with mycophenolic acid (MPA) or mycophenolate mofetil (MMF) plus steroids, with stable plasma levels of tacrolimus.
3. No clinical or histological immunological dysfunction before randomization
4. No de novo anti-HLA DSA at the time of randomization.
5. Patients who wish to and are able to give written informed consent to participate in the study.
6. For women, agreeing to use efficient contraception during the study.

Exclusion Criteria:

1. Patients who receive a multiorgan transplant.
2. Retransplants.
3. Presence of DSA before the transplant or at the time of randomization.
4. Cold ischemia time \>30 hours
5. Patients with serum creatinine \>2 mg/dL or proteinuria \>1g/day at the time of randomization
6. Prior episode of severe rejection (II-B-III in the Banff/13 classification) prior to randomization.
7. Presence of subclinical rejection on the protocol biopsy prior to randomization
8. Patients with BK-polyomavirus nephropathy at the time of randomization.
9. Patients with recurrent or de novo glomerulonephritis.
10. Patients who are being treated with immunosuppressive drugs other than those in the randomized clinical trial in question.
11. Patients who are positive for the human immunodeficiency virus (HIV) or those who have a severe systemic infection that, in the investigator's judgment, will require continued treatment.
12. Patients with any present or prior (during the previous 5 years) malignant disease, except basal or squamous cell carcinoma that has been excised.

Primary outcomes:
measure: Cases of Kidney Transplant Patients With DSA
timeFrame: 24 months
Secondary outcomes:
measure: Mean Score on the Protocol Biopsies in the Two Treatment Groups
timeFrame: 24 months
measure: Number of Participants With Acute Rejection Lesions
timeFrame: 24 months
measure: Incidence of Diabetes Mellitus
timeFrame: 24 months
measure: Lipid Profile
timeFrame: 24 months
measure: Blood Pressure
timeFrame: 24 months
measure: Renal Function
timeFrame: 24 months
measure: Assess the Adherence to Immunosuppressive Therapy in the Two Treatment Groups
timeFrame: At 24 months
measure: Patient Survival
timeFrame: 24 months
measure: Graft Survival
timeFrame: 24 months
measure: Renal Function
timeFrame: 24 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Vall d Hebron Hospital
city: Barcelona
country: Spain
facility: Bellvitge Hospital
city: Malaga
country: Spain
facility: Carlos Haya Hospital
city: Tenerife
country: Spain
facility: Canarias University Hospital
city: Valencia
country: Spain
facility: Dr. Peset Hospital
Study officials:
affiliation: Carlos Haya Hospital
name: Domingo Hernandez, PhD
role: PRINCIPAL_INVESTIGATOR
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