Study to Compare the Outcome of Receiving Continued Immunosuppression Versus Stopping Immunosuppression at 6 Months to Safely Prevent Human Leukocyte Antigen (HLA) Sensitization in Patients With Late Renal Graft Failure

A Multi-centre, Open, Prospective, Randomized, Parallel-group, 24-month Study to Compare the Outcome of Receiving Continued Immunosuppression Versus Stopping Immunosuppression at 6 Months to Safely Prevent Human Leukocyte Antigen (HLA) Sensitization in Patients With Late Renal Graft Failure

The goal of this clinical trial is to compare the degree of HLA sensitization at 2 years in patients with late renal graft failure (> 3 months) when receiving reduced immunosuppressant treatment versus stopping immunosuppression at 6 months.

The main question this study aims to answer is:

Does maintaining long-term immunosuppression in patients with a late renal graft failure (> 3 months) safely reduce the risk of HLA sensitization?

To answer this question, patients will be assigned to a control arm or investigational arm:

• Patients assigned to the control arm will receive standard treatment, in which immunosuppressant treatment is withdrawn after 6 months.
• Patients assigned to the investigatonal arm will continue immunosuppressant treatment at low doses for 2 years.

Patients recruited in this clinical trial will be followed for up to 2 years. During this time, patients will visit the clinic every 3 months for checkups and tests.

Study Overview

• Status: Recruiting
• Conditions: Graft Rejection; Renal Failure Chronic Requiring Dialysis; Graft Failure; Allograft; Renal Failure , Chronic
• Intervention / Treatment: Drug: Calcineurin inhibitor withdrawal at 6 months; Drug: Continue low dose calcineurin inhibitor (CNI)

• Study Type: Interventional
• Enrollment (Estimated): 202
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Francesc Moreso, MD, PhD; Phone Number: 93 489 30 00; Email: francescjosep.moreso@vallhebron.cat

Study Locations

• Spain
  • Barcelona, Spain, 0835
    • Recruiting
    • Hospital Universitario Vall d'Hebron
    • Contact: Francesc Moreso, MD, PhD; Phone Number: +34 93 489 30 00; Email: francescjosep.moreso@vallhebron.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient must be able to understand and provide written informed consent
• Patients older than 18 years who had received at least one previous renal transplant
• Patients with a retained kidney graft failed for any reason which survived at least 3 months
• Patients on dialysis, either hemodialysis or peritoneal dialysis. Patients can be on dialysis for a maximum of 6 months at the time of randomization, as long as the patients have taken an uninterrupted immunosuppressive regimen of calcineurin inhibitors (tacrolimus or cyclosporine) and steroids since dialysis was restarted
• Patients already relisted or candidates to relist to deceased donor kidney transplantation according to the treating physician criteria
• Patients taking immunosuppressants tacrolimus or cyclosporine
• cPRA at the time of randomization ≤ 90%

Exclusion Criteria:

• Patients who have received another solid organ transplantation (liver, lung, heart or pancreas)
• Patients waiting for a living related / unrelated kidney transplant
• Graft survival of the failed graft lower than 3 months
• Patients in dialysis more than 6 months at the time of randomization
• Patients not accomplishing criteria to relist in the transplantation list according to the treating physician criteria
• Pregnant women
• Females of childbearing age who have not used or do not plan to use acceptable birth control measures, for the duration of the study. Patients should use one of the acceptable birth control measures recommended in the document "Recommendations related to contraception and pregnancy testing in clinical trials" published by the Clinical Trials Facilitation and Coordination Group (CTFG) (version 1.1, published 21/09/2020). Recommended birth control measures include oral, injected or implanted hormonal contraceptive, barrier methods (condom or diaphragm with spermicide), intrauterine device, surgical sterilization, transdermal delivery, or sexual abstinence. If sexually active, the subject must have been using one of the accepted birth control methods at least one month prior to study entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Arm	Drug: Calcineurin inhibitor withdrawal at 6 months; CNI dose (tacrolimus or cyclosporine) will be reduced to one-half on month 3 visit and completely withdrawn on month 6 visit.
Active Comparator: Investigational arm	Drug: Continue low dose calcineurin inhibitor (CNI); CNI dose (tacrolimus or cyclosporine) will be adjusted to maintain low tacrolimus or cyclosporine whole blood trough levels from month 3 to month 24 or End of Study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Degree of HLA sensitization	The difference between the two treatment arms in the degree of HLA sensitization at 2-years measured as cPRA (%).	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality for any reason	The difference between the two treatment arms at 2-years on mortality for any reason	2 years
Days of hospitalization for any reason	The difference between the two treatment arms at 2-years on days of hospitalization for any reason	2 years
Percentage of patients effectively relisted during follow-up	The difference between the two treatment arms at 2-years on percentage of patients effectively relisted during follow-up	2 years
Percentage of patients transplanted	The difference between the two treatment arms at 2-years on percentage of patients transplanted	2 years
Percentage of patients delisted for any reason	The difference between the two treatment arms at 2-years on percentage of patients delisted for any reason	2 years
Incidence of infection	The difference between the two treatment arms at 2-years on incidence of infection	2 years
Incidence of cardiovascular events	The difference between the two treatment arms at 2-years on incidence of cardiovascular events	2 years
Incidence of cancer	The difference between the two treatment arms at 2-years on incidence of cancer	2 years
Incidence of graft-intolerance syndrome requiring graft nephrectomy or percutaneous embolization of the non-functioning graft	The difference between the two treatment arms at 2-years incidence of graft-intolerance syndrome requiring graft nephrectomy or percutaneous embolization of the non-functioning graft	2 years
Erythropoietin resistance index	The difference between the two treatment arms at 2-years on erythropoietin resistance index	2 years
Residual renal function	The difference between the two treatment arms at 2-years on residual renal function	2 years
Number of circulating memory B-cells	The difference between the two treatment arms at 2-years on number of circulating memory B-cells	2 years
Adverse events	The difference in the incidence of adverse events (AE) in the two treatment arms	2 years

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2024
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: November 5, 2024
• First Posted (Actual): November 6, 2024

Study Record Updates

• Last Update Posted (Actual): November 6, 2024
• Last Update Submitted That Met QC Criteria: November 5, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Renal failure; Graft failure; Calcineurin inhibitors; HLA sensitization; immunosuppressor
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Failure, Chronic; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Calcineurin Inhibitors
• Other Study ID Numbers: PREVSENSI; 2023-506879-98-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No