BEAT-BK: A Trial to Treat Polyomavirus Infections (BKPyV) in Kidney and Simultaneous Kidney Pancreas Transplant Recipients

Sponsor

The University of Queensland (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05325008

Collaborator

(none)

250

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

An adaptive, two-arm, RCT of immunosuppression reduction/modification (usual care) with and without IVIG in kidney and SPK recipients with BKPyV infections.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplant BK Viremia	Drug: Intravenous immunoglobulin	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

250 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

An Adaptive Randomised Controlled Trial to Treat Polyomavirus Infections (BKPyV) in Kidney and Kidney Pancreas Transplant Recipients

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2027

Anticipated Study Completion Date :

Nov 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Control Immunosuppression reduction/modification
Experimental: Interventional Immunosuppression reduction/modification + Intravenous Immunoglobulin infusion	Drug: Intravenous immunoglobulin Human immunoglobulin

Arm

Intervention/Treatment

No Intervention: Control

Immunosuppression reduction/modification

Experimental: Interventional

Immunosuppression reduction/modification + Intravenous Immunoglobulin infusion

Drug: Intravenous immunoglobulin

Human immunoglobulin

Outcome Measures

Primary Outcome Measures

To compare the efficacy of IVIG with standard of care on BKPyV infection in kidney and simultaneous kidney pancreas transplant recipients with polyomavirus infections (BKPyV) [12 weeks]
All randomized patients will be ranked based on 5 separate outcomes: death, graft loss, acute rejection, viraemia, eGFR decline, and immunosuppression load. The primary comparison of interest is the comparison of ranks between patients randomised to the IVIG arm and standard of care arm. eGFR will be estimated using the CKD-EPI formula for participants aged ≥ 18 years. The Schwartz equation will be used to estimate the eGFR for participants less than 18 years.

Secondary Outcome Measures

To assess the proportion of participants with a BKPyV viral load reduction of ≥ 3 log or an absolute value of <1000 copies/ml [12 weeks]
Measured by the viral count
To assess graft function catergorised as the proportion of participants with an eGFR decline ≥ 10 ml/min/1.73 m2 [12, 24 & 48 weeks]
Measured by CKD-EPI, Bedside Schwartz.
To compare mortality in participants with BKPyV between the intervention and control groups [12, 24 & 48 weeks]
Measured by mortality rate
To compare graft survival and death-censored graft survival in participants with BKPyV between the intervention and control groups [12, 24 & 48 weeks]
Not yet available
To compare the number of acute rejection (cellular and antibody mediated) episodes in participants with BKPyV between the intervention and control groups [12 & 48 weeks]
Measured through kidney transplant biopsy + donor specific antibodies
To compare the development of de novo donor-specific antibodies in participants with BKPyV between the intervention and control groups [12 weeks]
Measured by kidney transplant biopsy
To compare the incidence of infusion reactions and venous thromboembolism in participants with BKPyV between the intervention and control groups [12 weeks]
Not yet available

Other Outcome Measures

To compare the number of hospitalisations due to infection in participants with BKPyV between the intervention and control groups [weeks 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 48]
Measured by Hospitalisation (infection)
To compare the number of infectious events requiring antimicrobial (antibacterial, antiviral, antifungal, antiprotozoal) therapy in participants with BKPyV between the intervention and control groups [weeks 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 48]
Not yet available
To compare health-related quality of life in participants with BKPyV between the intervention and control groups [12, 24 & 48 weeks]
Measured by EQ-5D-5L
To compare the development of PyVAN in participants with BKPyV between the intervention and control groups [12 & 48 weeks]
Measured by the rate of other infections and cancer
To assess the long term composite ranked outcome in participants with BKPyV between the intervention and control groups [24 & 48 weeks]
Measured through composite ranked outcomes

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Aged 2 years or above
Have received a kidney or SPK transplant
Be able to provide informed consent
Have a sustained BKPyV-DNAemia (detected by RT-PCR with viral counts ≥ 1x10(3) copies per ml on two separate occasions at least 1 week

Exclusion Criteria:

Contraindications to receiving IVIG as a treatment
Diagnosed Hyperprolinemia
IgA deficiency with antibodies to IgA and a history of hypersensitivity
Guardians/caregivers (for children) unable to provide informed voluntary consent/assent
Participants with concurrent and active acute rejection
Participants whom treating clinicians would regard as unsafe to be enrolled
Participants with limited life expectancy (<12 months)