Other Complication of Kidney TransplantPhase 4NCT02284464

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

A Phase 4 study testing Prednisone withdrawal and Prednisone continuation in people with Other Complication of Kidney Transplant and Renal Transplant Rejection, run by Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud at 5 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Other Complication of Kidney Transplant, Renal Transplant Rejection
What is being tested?: Prednisone withdrawal and Prednisone continuation
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 230 participants
Where: 5 sitesSpain
Study dates: Feb 2015to Dec 2019
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.
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.
No clinical or histological immunological dysfunction before randomization
No de novo anti-HLA DSA at the time of randomization.
Patients who wish to and are able to give written informed consent to participate in the study.
For women, agreeing to use efficient contraception during the study.

Who cannot join

Patients who receive a multiorgan transplant.
Retransplants.
Presence of DSA before the transplant or at the time of randomization.
Cold ischemia time >30 hours
Patients with serum creatinine >2 mg/dL or proteinuria >1g/day at the time of randomization
Prior episode of severe rejection (II-B-III in the Banff/13 classification) prior to randomization.

Show all 12Show fewer

Presence of subclinical rejection on the protocol biopsy prior to randomization
Patients with BK-polyomavirus nephropathy at the time of randomization.
Patients with recurrent or de novo glomerulonephritis.
Patients who are being treated with immunosuppressive drugs other than those in the randomized clinical trial in question.
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.
Patients with any present or prior (during the previous 5 years) malignant disease, except basal or squamous cell carcinoma that has been excised.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

Spain5 sites

Vall d Hebron Hospital
Barcelona, 08035
Bellvitge Hospital
Barcelona, 08907
Carlos Haya Hospital
Málaga, 29010
Canarias University Hospital
Santa Cruz de Tenerife, 38200
Dr. Peset Hospital
Valencia, 46017

Other trials in Spain

About this study

Official title: Steroid Withdrawal and Novo Donor-specific Anti-HLA Antibodies in Renal Transplant Patients: a Prospective, Randomized and Controlled Study in Parallel Groups

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

Conditions: Other Complication of Kidney Transplant, Renal Transplant Rejection
Being tested: Prednisone withdrawal, Prednisone continuation
Keywords: Kidney transplant, Immunosuppression, Steroid withdrawal, Donor specific antibodies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Prednisone withdrawalDrug
Withdrawal of steroids
Prednisone continuationDrug
Continuation of steroids

Study groups in NCT02284464
Study group	Role	What they receive
Steroids, tacrolimus and mycophenolate	Active comparator	Normal treatment arm Receives: Drug: Prednisone continuation
Tacrolimus and mycophenolate	Experimental	Normal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs Receives: Drug: Prednisone withdrawal

What is being measured

The primary outcome is the main question the study is designed to answer.

Cases of Kidney Transplant Patients With DSA
Measurements of DSA at baseline, and at 3, 6, 12, 18 and 24 months
Measured: 24 months

Secondary outcomes (10)

Mean Score on the Protocol Biopsies in the Two Treatment Groups
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.
Measured: 24 months
Number of Participants With Acute Rejection Lesions
Patients with acute rejection lesions (including subclinical rejection) at 24 months according to Banff classification
Measured: 24 months
Incidence of Diabetes Mellitus
Incidence of diabetes mellitus after kidney transplant in both groups at 1, 2, 3, 4, 6, 9, 12, 18 and 24 months
Measured: 24 months
Lipid Profile
Lipid profile after kidney transplant in both groups at 24 months
Measured: 24 months
Blood Pressure
Blood pressure after kidney transplant in both groups at 24 months
Measured: 24 months
Renal Function
Renal function after kidney transplant in both groups at 24 months measured according to the creatinine (mg/dL) concentrations
Measured: 24 months
Assess the Adherence to Immunosuppressive Therapy in the Two Treatment Groups
The Basle scale was used to assess adherence (BAASIS questionnaire) to immunosuppressive therapy.
Measured: At 24 months
Patient Survival
Patient survival after kidney transplant in both groups
Measured: 24 months
Graft Survival
Graft survival after kidney transplant in both groups
Measured: 24 months
Renal Function
Renal function after kidney transplant in both groups at 24 months measured according to the proteinuria (mg/24 h) concentrations
Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2015Dec 2019

First posted6 Nov 2014 (estimated)
Study startFeb 2015
Primary completionJul 2019
Study completionDec 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (21)Papers the sponsor has linked to this study.
Other trials for Other Complication of Kidney TransplantStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 230 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02284464
Sponsor's protocol ID: EVITAESTEROIDE-12
Status last verified: Dec 2019
First submitted: 16 Oct 2014
Last updated: 14 Apr 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Miller LW. Cardiovascular toxicities of immunosuppressive agents. Am J Transplant. 2002 Oct;2(9):807-18. doi: 10.1034/j.1600-6143.2002.20902.x.
PubMed 12392286
Marcen R. Immunosuppressive drugs in kidney transplantation: impact on patient survival, and incidence of cardiovascular disease, malignancy and infection. Drugs. 2009 Nov 12;69(16):2227-43. doi: 10.2165/11319260-000000000-00000.
PubMed 19852526
Vincenti F, Schena FP, Paraskevas S, Hauser IA, Walker RG, Grinyo J; FREEDOM Study Group. A randomized, multicenter study of steroid avoidance, early steroid withdrawal or standard steroid therapy in kidney transplant recipients. Am J Transplant. 2008 Feb;8(2):307-16. doi: 10.1111/j.1600-6143.2007.02057.x.
PubMed 18211506
Arnol M, de Mattos AM, Chung JS, Prather JC, Mittalhenkle A, Norman DJ. Late steroid withdrawal and cardiovascular events in kidney transplant recipients. Transplantation. 2008 Dec 27;86(12):1844-8. doi: 10.1097/TP.0b013e31818ffec0.
PubMed 19104432
Opelz G, Dohler B. Association between steroid dosage and death with a functioning graft after kidney transplantation. Am J Transplant. 2013 Aug;13(8):2096-105. doi: 10.1111/ajt.12313. Epub 2013 Jun 10.
PubMed 23750878
Opelz G, Dohler B, Laux G; Collaborative Transplant Study. Long-term prospective study of steroid withdrawal in kidney and heart transplant recipients. Am J Transplant. 2005 Apr;5(4 Pt 1):720-8. doi: 10.1111/j.1600-6143.2004.00765.x.
PubMed 15760395
Gonzalez-Molina M, Gentil MA, Burgos D, Cabello M, Cobelo C, Bustamante J, Errasti P, Franco A, Hernandez D. Effect of long-term steroid withdrawal in renal transplant recipients: a retrospective cohort study. NDT Plus. 2010 Jun;3(Suppl_2):ii32-ii36. doi: 10.1093/ndtplus/sfq064.
PubMed 20508858
Kasiske BL, Chakkera HA, Louis TA, Ma JZ. A meta-analysis of immunosuppression withdrawal trials in renal transplantation. J Am Soc Nephrol. 2000 Oct;11(10):1910-1917. doi: 10.1681/ASN.V11101910.
PubMed 11004223
Pascual J, Quereda C, Zamora J, Hernandez D; Spanish Group for Evidence-Based Medicine in Renal Transplantation. Steroid withdrawal in renal transplant patients on triple therapy with a calcineurin inhibitor and mycophenolate mofetil: a meta-analysis of randomized, controlled trials. Transplantation. 2004 Nov 27;78(10):1548-56. doi: 10.1097/01.tp.0000140969.43761.1f.
PubMed 15599321
Woodle ES, First MR, Pirsch J, Shihab F, Gaber AO, Van Veldhuisen P; Astellas Corticosteroid Withdrawal Study Group. A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy. Ann Surg. 2008 Oct;248(4):564-77. doi: 10.1097/SLA.0b013e318187d1da.
PubMed 18936569
Terasaki PI, Ozawa M. Predicting kidney graft failure by HLA antibodies: a prospective trial. Am J Transplant. 2004 Mar;4(3):438-43. doi: 10.1111/j.1600-6143.2004.00360.x.
PubMed 14961999
Wiebe C, Gibson IW, Blydt-Hansen TD, Karpinski M, Ho J, Storsley LJ, Goldberg A, Birk PE, Rush DN, Nickerson PW. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant. 2012 May;12(5):1157-67. doi: 10.1111/j.1600-6143.2012.04013.x. Epub 2012 Mar 19.
PubMed 22429309
Gill JS, Landsberg D, Johnston O, Shapiro RJ, Magil AB, Wu V, Tinckam K, Keown P. Screening for de novo anti-human leukocyte antigen antibodies in nonsensitized kidney transplant recipients does not predict acute rejection. Transplantation. 2010 Jan 27;89(2):178-84. doi: 10.1097/TP.0b013e3181c3503e.
PubMed 20098280
Cantarovich D, De Amicis S, Akl A, Devys A, Vistoli F, Karam G, Soulillou JP. Posttransplant donor-specific anti-HLA antibodies negatively impact pancreas transplantation outcome. Am J Transplant. 2011 Dec;11(12):2737-46. doi: 10.1111/j.1600-6143.2011.03729.x. Epub 2011 Sep 11.
PubMed 21906255
Hoshino J, Kaneku H, Everly MJ, Greenland S, Terasaki PI. Using donor-specific antibodies to monitor the need for immunosuppression. Transplantation. 2012 Jun 15;93(11):1173-8. doi: 10.1097/TP.0b013e31824f3d7c.
PubMed 22592887

Study at a glance

From the registry record, last updated by the sponsor on 14 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Steroid Withdrawal and Novo Donor-specific Anti-HLA Antibodies in Renal Transplant Patients: a Prospective, Randomized and Controlled Study in Parallel Groups
ClinicalTrials.gov ID: NCT02284464
Acronym / sponsor ID: EVITAESTEROIDE-12
Conditions: Other Complication of Kidney Transplant, Renal Transplant Rejection
Keywords: Kidney transplant, Immunosuppression, Steroid withdrawal, Donor specific antibodies
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 230 participants (actual)
Lead sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y SaludUniversity, hospital or other
Collaborators: Sociedad Andaluza de Trasplantes de Organos y Tejidos
Study start: Feb 2015
Primary completion: Jul 2019 (actual)
Study completion: Dec 2019 (actual)
First posted: 6 Nov 2014 (estimated)
Results: Posted 14 Apr 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Steroids, tacrolimus and mycophenolate	Active comparator	Drug: Prednisone continuationNormal treatment arm
Tacrolimus and mycophenolate	Experimental	Drug: Prednisone withdrawalNormal treatment for first 90 days, then steroid withdrawal carrying on with the other drugs

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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.
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.
No clinical or histological immunological dysfunction before randomization
No de novo anti-HLA DSA at the time of randomization.
Patients who wish to and are able to give written informed consent to participate in the study.

Key exclusion criteria (12 listed)

Patients who receive a multiorgan transplant.
Retransplants.
Presence of DSA before the transplant or at the time of randomization.
Cold ischemia time >30 hours
Patients with serum creatinine >2 mg/dL or proteinuria >1g/day at the time of randomization

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Prednisone withdrawalWithdrawal of steroids	Drug	Tacrolimus and mycophenolate
Prednisone continuationContinuation of steroids	Drug	Steroids, tacrolimus and mycophenolate

Primary outcome

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

10 secondary outcomes

Mean Score on the Protocol Biopsies in the Two Treatment Groups
Time frame: 24 months
Number of Participants With Acute Rejection Lesions
Time frame: 24 months
Incidence of Diabetes Mellitus
Time frame: 24 months
Lipid Profile
Time frame: 24 months
Blood Pressure
Time frame: 24 months
Renal Function
Time frame: 24 months
Assess the Adherence to Immunosuppressive Therapy in the Two Treatment Groups
Time frame: At 24 months
Patient Survival
Time frame: 24 months
Graft Survival
Time frame: 24 months
Renal Function
Time frame: 24 months

Results and safety

Results posted to the registry on 14 Apr 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Steroids, Tacrolimus and Mycophenolate	52	39
Tacrolimus and Mycophenolate	53	36

Primary outcome: Cases of Kidney Transplant Patients With DSA

Time frame: 24 months. Count of participants. Unit: Participants

Measure	Steroids, Tacrolimus and Mycophenolate n = 39	Tacrolimus and Mycophenolate n = 36
Value	0	0

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: 24 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Steroids, Tacrolimus and Mycophenolate	10 of 52 (19.2%)	0 of 52 (0%)	0 of 52
Tacrolimus and Mycophenolate	15 of 53 (28.3%)	0 of 53 (0%)	0 of 53

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 12392286Miller LW. Cardiovascular toxicities of immunosuppressive agents. Am J Transplant. 2002 Oct;2(9):807-18. doi: 10.1034/j.1600-6143.2002.20902.x.
Background: PubMed 19852526Marcen R. Immunosuppressive drugs in kidney transplantation: impact on patient survival, and incidence of cardiovascular disease, malignancy and infection. Drugs. 2009 Nov 12;69(16):2227-43. doi: 10.2165/11319260-000000000-00000.
Background: PubMed 18211506Vincenti F, Schena FP, Paraskevas S, Hauser IA, Walker RG, Grinyo J; FREEDOM Study Group. A randomized, multicenter study of steroid avoidance, early steroid withdrawal or standard steroid therapy in kidney transplant recipients. Am J Transplant. 2008 Feb;8(2):307-16. doi: 10.1111/j.1600-6143.2007.02057.x.
Background: PubMed 19104432Arnol M, de Mattos AM, Chung JS, Prather JC, Mittalhenkle A, Norman DJ. Late steroid withdrawal and cardiovascular events in kidney transplant recipients. Transplantation. 2008 Dec 27;86(12):1844-8. doi: 10.1097/TP.0b013e31818ffec0.
Background: PubMed 23750878Opelz G, Dohler B. Association between steroid dosage and death with a functioning graft after kidney transplantation. Am J Transplant. 2013 Aug;13(8):2096-105. doi: 10.1111/ajt.12313. Epub 2013 Jun 10.
Background: PubMed 15760395Opelz G, Dohler B, Laux G; Collaborative Transplant Study. Long-term prospective study of steroid withdrawal in kidney and heart transplant recipients. Am J Transplant. 2005 Apr;5(4 Pt 1):720-8. doi: 10.1111/j.1600-6143.2004.00765.x.
Background: PubMed 20508858Gonzalez-Molina M, Gentil MA, Burgos D, Cabello M, Cobelo C, Bustamante J, Errasti P, Franco A, Hernandez D. Effect of long-term steroid withdrawal in renal transplant recipients: a retrospective cohort study. NDT Plus. 2010 Jun;3(Suppl_2):ii32-ii36. doi: 10.1093/ndtplus/sfq064.
Background: PubMed 11004223Kasiske BL, Chakkera HA, Louis TA, Ma JZ. A meta-analysis of immunosuppression withdrawal trials in renal transplantation. J Am Soc Nephrol. 2000 Oct;11(10):1910-1917. doi: 10.1681/ASN.V11101910.
Background: PubMed 15599321Pascual J, Quereda C, Zamora J, Hernandez D; Spanish Group for Evidence-Based Medicine in Renal Transplantation. Steroid withdrawal in renal transplant patients on triple therapy with a calcineurin inhibitor and mycophenolate mofetil: a meta-analysis of randomized, controlled trials. Transplantation. 2004 Nov 27;78(10):1548-56. doi: 10.1097/01.tp.0000140969.43761.1f.
Background: PubMed 18936569Woodle ES, First MR, Pirsch J, Shihab F, Gaber AO, Van Veldhuisen P; Astellas Corticosteroid Withdrawal Study Group. A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy. Ann Surg. 2008 Oct;248(4):564-77. doi: 10.1097/SLA.0b013e318187d1da.
Background: PubMed 14961999Terasaki PI, Ozawa M. Predicting kidney graft failure by HLA antibodies: a prospective trial. Am J Transplant. 2004 Mar;4(3):438-43. doi: 10.1111/j.1600-6143.2004.00360.x.
Background: PubMed 22429309Wiebe C, Gibson IW, Blydt-Hansen TD, Karpinski M, Ho J, Storsley LJ, Goldberg A, Birk PE, Rush DN, Nickerson PW. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant. 2012 May;12(5):1157-67. doi: 10.1111/j.1600-6143.2012.04013.x. Epub 2012 Mar 19.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Domingo Hernandez, PhD principal investigator

Carlos Haya Hospital

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cases of Kidney Transplant Patients With DSA (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02284464, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2020.