Immunosuppression Optimization Using The Prospera Assay In Kidney Transplant Recipients (IMPAKT)

Official title

Immunosuppressant optiMization Using the Prospera Assay in Kidney Transplant (IMPAKT) Randomized Controlled Trial

Overview

IMPAKT is a research study that looks at whether a blood test called Prospera™ can help doctors better adjust anti-rejection medications, compared to the usual way doctors manage these medications without using this test.

Detailed description

The IMPAKT study is a multi-center randomized controlled trial (RCT) in which stable low-risk kidney transplant (Tx) recipients receiving maintenance immunosuppression with tacrolimus, MPA dosage with or without corticosteroids will be randomized to the Immunosuppression optimization (Test) arm or the Standard of Care (SoC) Immunosuppression (Control) arm.

Participants will be enrolled at three months posttransplant and monitored with routine standard of care treatment and monthly Prospera blood draws from enrollment to 6 months posttransplant. All subjects will follow their center's SoC immunosuppressive therapy (IST) from enrollment to 6 months post-transplant. Subjects will be randomized at 6 months post-transplant to either the Test arm versus the Control arm.

The test arm will include participants who are managed with routine clinical care, along with a standardized dd-cfDNA protocol, to guide optimization of immunosuppression dosages. The control arm will include subjects who are managed with routine clinical care and receiving the standard of care (SoC) immunosuppression. This RCT will compare a hierarchical composite end point between the test and the control arm at 24 months post-transplant.

Interventions

• Diagnostic test Prospera Immunosuppression Optimization
  The test arm will include participants who are managed with routine clinical care, along with a standardized dd-cfDNA protocol, to guide optimization of immunosuppression dosages.

Primary outcome measures

• Tier 1: Compare the number of randomized participants who experienced death related to allograft, using a win ratio hierarchical endpoint [Time frame: From enrollment to 24 months post-transplant]
• Tier 2: Compare the number of randomized participants who experienced death censored graft loss (retransplant or return to dialysis), using a win ratio hierarchical endpoint [Time frame: From enrollment to 24 months post-transplant]
• Tier 3: Compare the number of randomized participants who experienced eGFR decline >30% between 6 and 24 months, using a win ratio hierarchical endpoint. [Time frame: From enrollment to 24 months post-transplant]
• Tier 4: Compare the number of randomized participants who experienced biopsy proven rejection requiring treatment with intravenous medications, using a win ratio hierarchical endpoint. [Time frame: From enrollment to 24 months post-transplant]
• Tier 5: Compare the number of randomized participants who experienced transplant-related hospitalization ≥2 nights not related to biopsy proven rejection, using a win ratio hierarchical endpoint. [Time frame: From enrollment to 24 months post-transplant]
• Tier 6: Compare the number of randomized participants who developed de novo DSA after 6 months, and by 24 months, using a win ratio hierarchical endpoint. [Time frame: From enrollment to 24 months post-transplant]
• Tier 7: Compare the number of randomized participants who experienced adverse outcome (AO), defined as GI Toxicity, Leukopenia, and/or Infection, using a win ratio hierarchical endpoint. [Time frame: From enrollment to 24 months post-transplant]

Eligibility criteria

Inclusion criteria

• Subjects received a kidney transplant in the prior 3 months.
• Subjects receiving maintenance therapy consisting of tacrolimus, mycophenolate sodium or mycophenolate mofetil, and optionally corticosteroids, at the time of enrollment.
• Subjects received induction therapy comprising IL2 receptor antagonist or thymoglobulin, or received no induction therapy.
• 18 years of age or older at time of signing informed consent.
• Able to read, understand and provide written informed consent, and willing and able to comply with the study requirements. If the subject is unable to sign the informed consent, a legally authorized representative (LAR) can consent on behalf of the subject.
• Subjects are at the site standard-of-care MPA dosage

Exclusion criteria

• Concurrent multiple solid organ or tissue transplants.
• History of a previous organ transplant (aside from present kidney transplant), or cellular transplant.
• DSA Positive according to local protocol, including either pre-transplant DSA positivity and de novo DSA positivity.
• Any prior dd-cfDNA results ≥1.0% or ≥78cp/mL after 28 days post-transplant.
• ABO Incompatible donor.
• A serious medical condition that may adversely affect ability to participate in the study (e.g, current diagnosis of cancer).
• Pregnancy.
• Received any induction therapy other than IL2 receptor antagonist or thymoglobulin.
• Receiving any maintenance immunosuppression other than tacrolimus, mycophenolate sodium or mycophenolate mofetil, and prednisone.
• Currently undergoing regular dialysis.
• Considered high-risk at the time of enrollment, as per the treating physician.
• Planned or ongoing use of other commercially available or investigational dd-cfDNA or blood-based gene expression profile assays for rejection surveillance, through randomization.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07718633 · 25-098-OH

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗