Clinical trial NCT05325008: A Trial to Treat Polyomavirus Infections (BKPyV) in Kidney and Simultaneous Kidney Pancreas Transplant Recipients
Official title: An Adaptive Randomised Controlled Trial to Treat Polyomavirus Infections (BKPyV) in Kidney and Kidney Pancreas Transplant Recipients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: BK Viremia
Kidney Transplant Infection
Kidney Transplant Failure and Rejection
Keywords: Kidney transplantation
Intravenous immunoglobulin
Virus
Nephropathy
Clinical trial
Nephrology
Lead sponsor: The University of Queensland
Sponsor class: OTHER
First posted: 2022-04-13
Enrollment: 280
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: Inclusion Criteria:

1. Aged 2 years or above
2. Have received a kidney or simultaneous pancreas-kidney transplant
3. 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.
4. Be able to provide informed consent or consent given by a parent or guardian (if age \<18 years) or other authorised person

Exclusion Criteria:

1. Contraindications to receiving IVIG as a treatment
2. Current active acute rejection (≤ 3 months prior)
3. Treating clinicians would regard as unsafe to be enrolled
4. Limited life expectancy (\< 12 months)
5. Receiving Belatacept as part of their immunosuppression protocol
6. Currently undergoing or who have previously received, viral-specific T-cell therapy for BK viremia
7. Prior infection and treatment for BKPyV-Viremia
8. Received IVIG treatment in the past with last IVIG treatment \< 4 weeks prior to randomisation

Primary outcomes:
measure: Composite ordinal outcome based on all cause death, allograft loss, eGFR decline, acute allograft rejection or BKV load > 1000 copies/mL, and immunosuppression load.
timeFrame: 11 - 13 weeks
Secondary outcomes:
measure: BKPyV final viral load
timeFrame: 12 weeks
measure: eGFR decline
timeFrame: 12, 24 & 48 weeks
measure: All cause death
timeFrame: 12, 24 & 48 weeks
measure: Graft loss
timeFrame: 12, 24 & 48 weeks
measure: Acute rejection of kidney and/or pancreas allografts
timeFrame: 12 & 48 weeks
measure: Donor Specific Anti-HLA Antibody
timeFrame: 12 & 48 weeks
measure: Infusion reactions and/ or venous thromboembolism events
timeFrame: 12 weeks
measure: Hospitalisations due to infection events
timeFrame: Baseline,1,2,3,4,5,6,7,8,10,12,24,48 weeks
measure: Number of infectious events requiring antimicrobial (antibacterial, antiviral, antifungal, antiprotozoal) therapy.
timeFrame: Baseline,1,2,3,4,5,6,7,8,10,12,24,48 weeks
measure: EuroQol-5 Dimension-5 Level for adults/ Health Utilities Index-3 for children
timeFrame: Baseline, 12, 24 & 48 weeks
measure: BK polyomavirus associated nephropathy events
timeFrame: 12 & 48 weeks
measure: Any cancer diagnosis or cancer related death
timeFrame: 24 & 48 weeks
measure: Composite ranked outcome
timeFrame: 24 & 48 weeks
measure: Adverse events of special interest and serious adverse events
timeFrame: Baseline,1,2,3,4,5,6,7,8,10,12,24,48 weeks
Other outcomes:
Locations:
city: Canberra
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: New Lambton Heights
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Sydney
country: Australia
facility: The Childrens Hospital Westmead
state: New South Wales
city: Westmead
country: Australia
facility: Western Sydney Local Health District (Westmead Hospital)
state: New South Wales
city: Brisbane
country: Australia
facility: Queensland Children's Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Melbourne
country: Australia
facility: Monash Health
state: Victoria
city: Perth
country: Australia
facility: Perth Children's Hospital
state: Western Australia
city: Perth
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
Study officials:
affiliation: University of Sydney
name: Germaine Wong, Professor
role: STUDY_CHAIR
References: