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

Kidney Transplant Infection Clinical Trial

— BEAT-BK  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05325008
• Other study ID #: 20.07
• Status: Recruiting
• Phase: Phase 3
• Start date: August 18, 2023
• Est. completion date: June 30, 2029

Study information

• Verified date: August 2023
• Source: The University of Queensland
• Contact: David Charman
• Phone: +61 498 521 400
• Email: beat-bk[@]uq.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 280
• Est. completion date: June 30, 2029
• Est. primary completion date: August 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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

Related Conditions & MeSH terms

• BK Viremia
• Communicable Diseases
• Infections
• Kidney Transplant Failure and Rejection
• Kidney Transplant Infection
• Polyomavirus Infections
• Viremia

Intervention

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.

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Adelaide	South Australia
Australia	Canberra Hospital	Canberra	Australian Capital Territory
Australia	Monash Health	Melbourne	Victoria
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Western Sydney Local Health District (Westmead Hospital)	Westmead	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland

Sponsors (1)

Lead Sponsor	Collaborator
The University of Queensland

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	11 - 13 weeks
Secondary	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	12 weeks
Secondary	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	12, 24 & 48 weeks
Secondary	All cause death	Compare the mortality rate in the intervention and control groups.	12, 24 & 48 weeks
Secondary	Graft loss	Compare the number of graft survival and death-censored graft survival participants in the intervention and control groups.	12, 24 & 48 weeks
Secondary	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.	12 & 48 weeks
Secondary	Donor Specific Anti-HLA Antibody	Compare the number of participants that develop de novo donor-specific antibodies between the intervention and control groups	12 & 48 weeks
Secondary	Infusion reactions and/ or venous thromboembolism events	Compare the incidence rate (number) of infusion reactions and venous thromboembolism between the intervention and control groups	12 weeks
Secondary	Hospitalisations due to infection events	Compare the number of hospitalisation due to infection between the intervention and control groups.	Baseline,1,2,3,4,5,6,7,8,10,12,24,48 weeks
Secondary	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	Baseline,1,2,3,4,5,6,7,8,10,12,24,48 weeks
Secondary	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.	Baseline, 12, 24 & 48 weeks
Secondary	BK polyomavirus associated nephropathy events	Compare the number of participants that develop BK polyomavirus associated nephropathy between the intervention and control groups	12 & 48 weeks
Secondary	Any cancer diagnosis or cancer related death	Compare the incidence rate (number) of cancer outcomes between the intervention and control groups.	24 & 48 weeks
Secondary	Composite ranked outcome	Compare the long-term composite ranked outcome between the intervention and control groups	24 & 48 weeks
Secondary	Adverse events of special interest and serious adverse events	Compare the incidence rate (number) of safety related events between intervention and control group.	Baseline,1,2,3,4,5,6,7,8,10,12,24,48 weeks