A Phase 2 interventional study of ACEi / ARB, SGLT2i, finerenone, semaglutide, pentoxifylline, hydrochlorthiazide, baricitinib in Diabetic Kidney Disease, sponsored by Iain Bressendorff. Terminated at 1 site in Denmark. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-09-25.
Sponsored by Iain Bressendorff · Phase 2, Interventional, and Treatment
The purpose of this trial is to investigate the feasibility and safety of implementing a protocol-based treatment aggressively targeting albuminuria in subjects with biopsy-proven diabetic nephropathy and severely elevated albuminuria. If this approach is feasible, the results of the trial will inform the design of a large-scale randomized clinical trial to evaluate the effect of this treatment on hard kidney endpoints (initiation of dialysis, kidney transplantation, and death from kidney failure) in subjects with biopsy-proven diabetic nephropathy and severely elevated albuminuria.
Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD) worldwide and declining kidney function is associated with a graded increase in the risk of death or hospitalization. Thus, prevention of kidney disease progression is of vital importance to prevent excess morbidity and mortality among people with DKD.
Increasing levels of albuminuria in patients with DKD are associated with a graded increase in the risk of developing ESKD and among patients with nephrotic-range albuminuria (i.e. > 2.000 mg/day) progressive decline in kidney function is particularly rapid. The currently available drugs which have demonstrated delayed progression to ESKD in DKD (captopril, losartan and irbesartan, canagliflozin, dapagliflozin, empagliflozin, and finerenone) all reduce albuminuria independently of blood pressure reductions, but it has long been debated whether reductions in albuminuria by itself reflects a reduction in the risk of ESKD or whether this is simply a by-product of treatment. Whether interventions targeting reductions in albuminuria reduce the incidence of ESKD has not been formally tested in a randomized controlled trial of hard kidney endpoints (e.g. initiation of dialysis, kidney transplantation or death from kidney disease).
We wish to conduct a randomized controlled trial in which we will test whether an aggressive treatment strategy of lowering albuminuria reduces the incidence of hard kidney endpoints compared to standard-of-care among patients with nephrotic-range albuminuria and very high risk of progression to ESKD. However, prior to conducting such a trial it is necessary first to test whether it is even possible to sufficiently lower albuminuria by these means. Therefore, we wish to first conduct a pilot trial to investigate the feasibility of such an approach.
Participants will be randomized 1:1 to standard-of-care or an albuminuria-reduction protocol. In the albuminuria-reduction protocol, subjects will be treated with various drugs that have all been shown to reduce albuminuria in DKD (although not all have been shown to reduce hard kidney outcomes). At each monthly study visit, drugs will be added or withdrawn in an attempt to maximally reduce albuminuria. Drugs that reduce albuminuria by \<10% since the last study visit will be discontinued. Drugs that successfully reduce albuminuria by >10% will be continued and further drugs will be added.
After 9 months subjects will discontinue protocol drugs and resume their previous medical care.
3,840 studies on the registry are indexed under Kidney Diseases; 500 are open to participants now.
This study's enrollment of 1 is below the median of 70 across 2,640 interventional studies indexed under Kidney Diseases.
Browse Kidney Diseases studies →Iain Bressendorff is the lead sponsor of 4 studies on the registry; 2 are open to participants now.
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Exclusion Criteria:
Maximally tolerated dose of ACEi or ARB (but not both), SGLT2i, and finerenone. Blood pressure target \<130/80 mm Hg
Drug: ACEi / ARB, SGLT2i, finerenone, semaglutide, pentoxifylline, hydrochlorthiazide, baricitinib
Maximally tolerated dose of ACEi or ARB (but not both), SGLT2i, and finerenone. Thereafter addition of semaglutide, pentoxifylline, hydrochlorothiazide, and baricitinib. Blood pressure target \<130/80 mm Hg, but if still UACR \>300 further reduction in blood pressure will be attempted as tolerated.
Drug: ACEi / ARB, SGLT2i, finerenone, semaglutide, pentoxifylline, hydrochlorthiazide, baricitinib
Standard of care for diabetic kidney disease.
urine albumin/creatinin-ratio (UACR) reduction to less than 50% of baseline
number of subjects achieving this endpoint
Time frame: after 9 months of treatment
UACR reduction to less than 70% of baseline
number of subjects achieving this endpoint
Time frame: after 9 months of treatment
UACR less than 300
number of subjects achieving this endpoint
Time frame: after 9 months of treatment
difference in UACR
between-groups difference in UACR
Time frame: after 9 months of treatment
difference in UACR
between-groups difference in UACR
Time frame: after 10 months of treatment (1 month off study drugs)
difference in eGFR
between-groups difference in eGFR
Time frame: after 9 months of treatment
difference in eGFR
between-groups difference in eGFR
Time frame: after 10 months of treatment (1 month off study drugs)
difference in systolic and diastolic blood pressure
between-groups difference in blood pressure
Time frame: after 9 months of treatment
difference in systolic and diastolic blood pressure
between-groups difference in blood pressure
Time frame: after 10 months of treatment (1 month off study drugs)
incidence of plasma potassium >5.5 mmol/L
number of subjects achieving this endpoint
Time frame: after 9 months of treatment
incidence of plasma potassium >6.0 mmol/L
number of subjects achieving this endpoint
Time frame: after 9 months of treatment
incidence of symptomatic hypotension
number of subjects achieving this endpoint
Time frame: after 9 months of treatment
Plan to share: No
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This study is terminated, as verified in Sep 2024. You cannot join it, but the record below documents what was studied.
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Iain Bressendorff