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

Phase 4

Completed

• Conditions: Renal Transplant Rejection; Other Complication of Kidney Transplant
• Interventions: Drug: Prednisone withdrawal; Drug: Prednisone continuation

• Registration Number: NCT02284464
• Lead Sponsor: 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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-10-16
• Study First Submitted QC: 2014-11-03
• Study First Posted: 2014-11-06
• Study Start: 2015-02
• Primary Completion: 2019-07
• Status Verified: 2019-12
• Study Completion: 2019-12
• Results First Submitted: 2020-01-16
• Results First Submitted QC: 2020-04-02
• Last Update Submitted: 2020-04-02
• Results First Posted: 2020-04-14
• Last Update Posted: 2020-04-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 230

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tacrolimus and mycophenolate	Prednisone withdrawal	Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs
Steroids, tacrolimus and mycophenolate	Prednisone continuation	Normal treatment arm

Primary Outcome Measures

Name	Time	Method
Cases of Kidney Transplant Patients With DSA	24 months	Measurements of DSA at baseline, and at 3, 6, 12, 18 and 24 months

Secondary Outcome Measures

Name	Time	Method
Renal Function	24 months	Renal function after kidney transplant in both groups at 24 months measured according to the proteinuria (mg/24 h) concentrations
Patient Survival	24 months	Patient survival after kidney transplant in both groups
Mean Score on the Protocol Biopsies in the Two Treatment Groups	24 months	Measurement at 24 months according to the Banff classification. The Banff Classification of Allograft Pathology is an international consensus classification for the reporting of biopsies from solid organ transplant. The scale ranges from 0 to 3, 3 being the worst.
Lipid Profile	24 months	Lipid profile after kidney transplant in both groups at 24 months
Blood Pressure	24 months	Blood pressure after kidney transplant in both groups at 24 months
Assess the Adherence to Immunosuppressive Therapy in the Two Treatment Groups	At 24 months	The Basle scale was used to assess adherence (BAASIS questionnaire) to immunosuppressive therapy.
Number of Participants With Acute Rejection Lesions	24 months	Patients with acute rejection lesions (including subclinical rejection) at 24 months according to Banff classification
Incidence of Diabetes Mellitus	24 months	Incidence of diabetes mellitus after kidney transplant in both groups at 1, 2, 3, 4, 6, 9, 12, 18 and 24 months
Graft Survival	24 months	Graft survival after kidney transplant in both groups

Trial Locations

Locations (5)

Dr. Peset Hospital; 🇪🇸 Valencia, Spain

Bellvitge Hospital; 🇪🇸 Barcelona, Spain

Vall d Hebron Hospital; 🇪🇸 Barcelona, Spain

Carlos Haya Hospital; 🇪🇸 Malaga, Spain

Canarias University Hospital; 🇪🇸 Tenerife, Spain