A Trial to Treat Polyomavirus Infections (BKPyV) in Kidney and Simultaneous Kidney Pancreas Transplant Recipients
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Immunosuppression reduction/modification + intravenous immunoglobulin, Immunosuppression reduction/modification.
- Who it may be relevant to
- Registry conditions: BK Viremia, Kidney Transplant Infection, Kidney Transplant Failure and Rejection. Basic parameters: from 2 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Australia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
An Adaptive Randomised Controlled Trial to Treat Polyomavirus Infections (BKPyV) in Kidney and Kidney Pancreas Transplant Recipients
Overview
BEAT-BK will see the effect of immunosuppression reduction/modification with and without IVIG on BKPyV infection, allograft function, allograft loss, acute transplant rejection, immunosuppression load and death in kidney and simultaneous kidney pancreas transplant recipients with polyomavirus infections (BKPyV).
Detailed description
BKPyV infection is a rare but also devastating disease in kidney and SPK transplant recipients. Immunosuppression used in transplantation minimises the risk of acute rejection and eventual graft loss, but suppression of the immune system increases the risk of opportunistic infections and reactivation of latent viruses causing disease, such as BKPyV infection. Therefore, balancing the complications of excessive versus inadequate immunosuppression is a key priority for patients and health professionals. The BEAT-BK trial is designed through a structured, consensus process, and informed by the pilot observational data generated by the investigators. The conventional immunosuppression reduction approach may include judicious reduction in the doses of calcineurin inhibitors and anti-proliferative agents, or conversion to less potent immunosuppression therapy such as a switch from tacrolimus to cyclosporine, or mycophenolate to azathioprine. While adjuvant therapy is not commonly used, 63% of participants would consider IVIG as a 'rescue', when conventional therapy has failed, or the graft function is deteriorating rapidly. IVIG is a nondepleting agent containing natural antibodies with potential antiviral and immunomodulatory properties. It is used against some chronic infections (Epstein-Barr virus) and the treatment of antibody-mediated rejection in kidney transplantation. In BKPyV infection, the certainty of the evidence for IVIG is very low due to imprecision, and high risk of bias (small, case series, retrospective cohorts), but it holds promise based on findings from our observational data (n = 50). Recipients with BKPyV-DNAemia who received IVIG as adjuvant therapy were more likely to achieve complete viral clearance at 12 months (77.3% vs. 33.3%, p \< 0.01) and less likely to relapse (11% vs. 27.3%, p=0.01) compared to recipients who received conventional therapy alone.
Interventions
- Drug Immunosuppression reduction/modification + intravenous immunoglobulin
Participants will receive intravenous immunoglobulin along with immunosuppression reduction/modification. - Other Immunosuppression reduction/modification
Participants will receive immunosuppression reduction/modification.
Primary outcome measures
- Composite ordinal outcome based on all cause death, allograft loss, eGFR decline, acute allograft rejection or BKV load > 1000 copies/mL, and immunosuppression load. [Time frame: 11 - 13 weeks]
Secondary outcome measures (12)
- BKPyV final viral load [Time frame: 12 weeks]
- eGFR decline [Time frame: 12, 24 & 48 weeks]
- All cause death [Time frame: 12, 24 & 48 weeks]
- Graft loss [Time frame: 12, 24 & 48 weeks]
- Acute rejection of kidney and/or pancreas allografts [Time frame: 12 & 48 weeks]
- Donor Specific Anti-HLA Antibody [Time frame: 12 & 48 weeks]
- Infusion reactions and/ or venous thromboembolism events [Time frame: 12 weeks]
- Hospitalisations due to infection events [Time frame: Baseline,1,2,3,4,5,6,7,8,10,12,24,48 weeks]
- Number of infectious events requiring antimicrobial (antibacterial, antiviral, antifungal, antiprotozoal) therapy. [Time frame: Baseline,1,2,3,4,5,6,7,8,10,12,24,48 weeks]
- EuroQol-5 Dimension-5 Level for adults/ Health Utilities Index-3 for children [Time frame: Baseline, 12, 24 & 48 weeks]
- BK polyomavirus associated nephropathy events [Time frame: 12 & 48 weeks]
- Any cancer diagnosis or cancer related death [Time frame: 24 & 48 weeks]
Eligibility criteria
Inclusion criteria
- Aged 2 years or above
- Have received a kidney or simultaneous pancreas-kidney transplant
- Have BKPyV-Viremia (detected by RT-PCR) with a viral count ≥ 5,000 copies per mL, or histological confirmation of BKPyVAN, within 3 weeks prior to randomisation.
- Be able to provide informed consent or consent given by a parent or guardian (if age <18 years) or other authorised person
Exclusion criteria
- Contraindications to receiving IVIG as a treatment
- Current active acute rejection (≤ 3 months prior)
- Treating clinicians would regard as unsafe to be enrolled
- Limited life expectancy (< 12 months)
- Receiving Belatacept as part of their immunosuppression protocol
- Currently undergoing or who have previously received, viral-specific T-cell therapy for BK viremia
- Prior infection and treatment for BKPyV-Viremia
- Received IVIG treatment in the past with last IVIG treatment < 4 weeks prior to randomisation
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
- Single blind
- Primary purpose
- Treatment
Study locations
Australia · 13 centers
- Canberra Hospital — Canberra
- John Hunter Hospital — New Lambton Heights
- Prince of Wales Hospital — Randwick
- Royal Prince Alfred Hospital — Sydney
- The Childrens Hospital Westmead — Sydney
- Western Sydney Local Health District (Westmead Hospital) — Westmead
- Queensland Children's Hospital — Brisbane
- Townsville University Hospital — Townsville
- … and 5 more centers
Publications
- Helle F, Aubry A, Morel V, Descamps V, Demey B, Brochot E. Neutralizing Antibodies Targeting BK Polyomavirus: Clinical Importance and Therapeutic Potential for Kidney Transplant Recipients. J Am Soc Nephrol. 2024 Oct 1;35(10):1425-1433. doi: 10.1681/ASN.0000000000000457. Epub 2024 Jul 9. PMID 39352862
Identifiers
NCT: NCT05325008 · AKTN 20.07