ClinicalTrials.gov
ClinicalTrials.gov Menu

Steroid Withdrawal and Donor-specific Anti-HLA Antibodies in Renal Transplant Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02284464
Recruitment Status : Active, not recruiting
First Posted : November 6, 2014
Last Update Posted : August 9, 2018
Sponsor:
Collaborator:
Sociedad Andaluza de Trasplantes de Organos y Tejidos
Information provided by (Responsible Party):
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud

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

Condition or disease Intervention/treatment Phase
Other Complication of Kidney Transplant Renal Transplant Rejection Drug: Prednisone withdrawal Drug: Prednisone continuation Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : February 2015
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Steroids, tacrolimus and mycophenolate
Normal treatment arm
Drug: Prednisone continuation
Continuation of steroids

Experimental: Tacrolimus and mycophenolate
Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs
Drug: Prednisone withdrawal
Withdrawal of steroids




Primary Outcome Measures :
  1. Cumulative incidence of kidney transplant patients with DSA [ Time Frame: 24 months ]
    Measurements of DSA at baseline, and at 3, 6, 12, 18 and 24 months


Secondary Outcome Measures :
  1. Interstitial fibrosis and tubular atrophy in both groups as well as vascular lesions in the graft.treatment groups [ Time Frame: 24 months ]
    Measurement at 3 and 24 months

  2. Acute rejection lesions [ Time Frame: 24 months ]
    Acute rejection lesions (including subclinical rejection) at 12 and 24 months according to Banff 2013 classification

  3. Incidence of diabetes mellitus [ Time Frame: 24 months ]
    Incidence of diabetes mellitus after kidney transplant in both groups at 1, 2, 3, 4, 6, 9, 12, 18 and 24 months

  4. Incidence of dyslipidemia [ Time Frame: 24 months ]
    Incidence of dyslipidemia after kidney transplant in both groups at 1, 2, 3, 4, 6, 9, 12, 18 and 24 months

  5. Incidence of hypertension [ Time Frame: 24 months ]
    Incidence of hypertension after kidney transplant in both groups at 1, 2, 3, 4, 6, 9, 12, 18 and 24 months

  6. Renal function [ Time Frame: 24 months ]
    Renal function after kidney transplant in both groups at 1, 2, 3, 4, 6, 9, 12, 18 and 24 months

  7. Assess the adherence to immunosuppressive therapy in the two treatment groups and its impact on the generation of DSA [ Time Frame: At 3, 12 and 24 months ]
  8. Patient survival [ Time Frame: 24 months ]
    Patient survival after kidney transplant in both groups

  9. Graft survival [ Time Frame: 24 months ]
    Graft survival after kidney transplant in both groups



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 or borderline lesions 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02284464


Locations
Spain
Vall d Hebron Hospital
Barcelona, Spain, 08035
Carlos Haya Hospital
Malaga, Spain, 29010
Canarias University Hospital
Tenerife, Spain, 38200
Sponsors and Collaborators
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
Sociedad Andaluza de Trasplantes de Organos y Tejidos
Investigators
Principal Investigator: Domingo Hernandez, PhD Carlos Haya Hospital

Publications:

Responsible Party: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
ClinicalTrials.gov Identifier: NCT02284464     History of Changes
Other Study ID Numbers: EVITAESTEROIDE-12
First Posted: November 6, 2014    Key Record Dates
Last Update Posted: August 9, 2018
Last Verified: February 2018

Keywords provided by Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud:
Kidney transplant
Immunosuppression
Steroid withdrawal
Donor specific antibodies

Additional relevant MeSH terms:
Antibodies
Immunoglobulins
Tacrolimus
Prednisone
Immunologic Factors
Physiological Effects of Drugs
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunosuppressive Agents
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action