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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
280
Participants will receive intravenous immunoglobulin along with immunosuppression reduction/modification.
Participants will receive immunosuppression reduction/modification.
Canberra Hospital
Canberra, Australian Capital Territory, Australia
RECRUITINGJohn Hunter Hospital
New Lambton Heights, New South Wales, Australia
RECRUITINGPrince of Wales Hospital
Randwick, New South Wales, Australia
RECRUITINGRoyal Prince Alfred Hospital
Sydney, New South Wales, Australia
RECRUITINGThe Childrens Hospital Westmead
Sydney, New South Wales, Australia
RECRUITINGWestern Sydney Local Health District (Westmead Hospital)
Westmead, New South Wales, Australia
RECRUITINGQueensland Children's Hospital
Brisbane, Queensland, Australia
RECRUITINGPrincess Alexandra Hospital
Woolloongabba, Queensland, Australia
RECRUITINGFlinders Medical Centre
Adelaide, South Australia, Australia
RECRUITINGMonash Health
Melbourne, Victoria, Australia
RECRUITING...and 2 more locations
Composite ordinal outcome based on all cause death, allograft loss, eGFR decline, acute allograft rejection or BKV load > 1000 copies/mL, and immunosuppression load.
All participants will be allocated a rank at 12 weeks between rank 5 (worst) and rank 1 (best). The primary comparison of interest is between participants randomised to intravenous immunoglobulin (IVIG) and participants randomised to the control arm. Outcome measures include: Rank 5 - all cause death, allograft loss, eGFR decline ≥10mls/min 1.73². Rank 4 - acute allograft rejection or BK viral load to \>1000 copies/mL. Ranks 3, 2, and 1 - the degree of immunosuppression reduction relative to baseline immunosuppression.
Time frame: 11 - 13 weeks
BKPyV final viral load
Compare the number of participants in the intervention and control groups with a BK Polyomavirus viral load to \<1000 copies/mL
Time frame: 12 weeks
eGFR decline
Compare the number of participants in the intervention and control groups with an estimated glomerular filtration rate (eGFR) decline ≥ 10 ml/min/1.73 m2
Time frame: 12, 24 & 48 weeks
All cause death
Compare the mortality rate in the intervention and control groups.
Time frame: 12, 24 & 48 weeks
Graft loss
Compare the number of graft survival and death-censored graft survival participants in the intervention and control groups.
Time frame: 12, 24 & 48 weeks
Acute rejection of kidney and/or pancreas allografts
Compare the number of acute rejections (cellular and antibody mediated) episodes between the intervention and control groups.
Time frame: 12 & 48 weeks
Donor Specific Anti-HLA Antibody
Compare the number of participants that develop de novo donor-specific antibodies between the intervention and control groups
Time frame: 12 & 48 weeks
Infusion reactions and/ or venous thromboembolism events
Compare the incidence rate (number) of infusion reactions and venous thromboembolism between the intervention and control groups
Time frame: 12 weeks
Hospitalisations due to infection events
Compare the number of hospitalisation due to infection between the intervention and control groups.
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.
Compare the number of infectious events requiring antimicrobial therapy between the intervention and control groups
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
Compare the outcomes of health-related quality of life between the intervention and control groups.
Time frame: Baseline, 12, 24 & 48 weeks
BK polyomavirus associated nephropathy events
Compare the number of participants that develop BK polyomavirus associated nephropathy between the intervention and control groups
Time frame: 12 & 48 weeks
Any cancer diagnosis or cancer related death
Compare the incidence rate (number) of cancer outcomes between the intervention and control groups.
Time frame: 24 & 48 weeks
Composite ranked outcome
Compare the long-term composite ranked outcome between the intervention and control groups
Time frame: 24 & 48 weeks
Adverse events of special interest and serious adverse events
Compare the incidence rate (number) of safety related events between intervention and control group.
Time frame: Baseline,1,2,3,4,5,6,7,8,10,12,24,48 weeks
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