Diabetic Kidney DiseasePhase 2WP3NCT05897372
Feasibility of Aggressive Albuminuria Reduction in Biopsy-Proven Diabetic Nephropathy - a Pilot Study
A Phase 2 study testing ACEi / ARB, SGLT2i, finerenone, semaglutide, pentoxifylline, hydrochlorthiazide, baricitinib in people with Diabetic Kidney Disease, run by Iain Bressendorff at 1 site in Denmark.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Kidney Disease
- What is being tested?
- ACEi / ARB, SGLT2i, finerenone, semaglutide, pentoxifylline, hydrochlorthiazide, baricitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Aug 2023to 23 Sep 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Diagnosis of diabetes mellitus type 2 (American Diabetes Association / European Association for the Study of Diabetes (ADA/EASD) definition)10
- Biopsy-proven diabetic nephropathy
- UACR ≥ 2,000 mg/g or
- UACR ≥ 1,500 mg/g if treated with sodium-glucose cotransporter 2 inhibitor (SGLT2i)
- Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2
- Negative pregnancy test and use of highly effective and safe contraception
- Able to give informed consent.
Who cannot join
- Kidney transplant recipient
- Findings on kidney biopsy suggestive of other or concomitant glomerulonephritis (findings associated with hypertensive nephropathy are not exclusion criteria).
- Plasma potassium at baseline > 5.2 mmol/L.
- Active malignancy (basal or squamous cell skin carcinoma, localised prostate cancer, and cancer with no signs of reoccurrence after 5 years are exempt from this).
- Systolic heart failure with NYHA class III-IV.
- Liver failure classified as Child-Pugh C.
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- Primary hyperaldosteronism.
- Previous cerebral or retinal haemorrhage.
- Biliary obstructive disorders.
- Acute myocardial infarction within the last three months.
- Severe cardiac arrhythmias.
- Clinically active gout.
- Plasma sodium at baseline < 135 mmol/L.
- Other diseases or conditions, which, in the opinion of the site investigator, would prevent participation in or completion of the trial.
- Treatment with potent CYP3A4 inhibitors.
- Participation in other interventional trials.
- Allergy towards one of more of the drugs to be used during the trial
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Nephrology, Herlev and Gentofte Hospital
Herlev, 2730
About this study
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.
Read the detailed description
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.
- Conditions
- Diabetic Kidney Disease
- Being tested
- ACEi / ARB, SGLT2i, finerenone, semaglutide, pentoxifylline, hydrochlorthiazide, baricitinib
- Medical subject headings
- Diabetic Nephropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACEi / ARB, SGLT2i, finerenone, semaglutide, pentoxifylline, hydrochlorthiazide, baricitinibDrug
Standard of care for diabetic kidney disease.
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care | Active comparator | Maximally tolerated dose of ACEi or ARB (but not both), SGLT2i, and finerenone. Blood pressure target <130/80 mm Hg Receives: Drug: ACEi / ARB, SGLT2i, finerenone, semaglutide, pentoxifylline, hydrochlorthiazide, baricitinib |
| Albuminuria-reduction protocol | Experimental | 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. Receives: Drug: ACEi / ARB, SGLT2i, finerenone, semaglutide, pentoxifylline, hydrochlorthiazide, baricitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
urine albumin/creatinin-ratio (UACR) reduction to less than 50% of baseline
number of subjects achieving this endpoint
Measured: after 9 months of treatment
Secondary outcomes (11)
UACR reduction to less than 70% of baseline
number of subjects achieving this endpoint
Measured: after 9 months of treatment
UACR less than 300
number of subjects achieving this endpoint
Measured: after 9 months of treatment
difference in UACR
between-groups difference in UACR
Measured: after 9 months of treatment
difference in UACR
between-groups difference in UACR
Measured: after 10 months of treatment (1 month off study drugs)
difference in eGFR
between-groups difference in eGFR
Measured: after 9 months of treatment
difference in eGFR
between-groups difference in eGFR
Measured: after 10 months of treatment (1 month off study drugs)
difference in systolic and diastolic blood pressure
between-groups difference in blood pressure
Measured: after 9 months of treatment
difference in systolic and diastolic blood pressure
between-groups difference in blood pressure
Measured: after 10 months of treatment (1 month off study drugs)
incidence of plasma potassium >5.5 mmol/L
number of subjects achieving this endpoint
Measured: after 9 months of treatment
incidence of plasma potassium >6.0 mmol/L
number of subjects achieving this endpoint
Measured: after 9 months of treatment
incidence of symptomatic hypotension
number of subjects achieving this endpoint
Measured: after 9 months of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2023
- Study start1 Aug 2023
- Primary completion23 Sep 2024
- Study completion23 Sep 2024
Why it stopped: Slow recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic Kidney DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, controlled, open-label, parallel-group, clinical trial.
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Iain Bressendorff
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Iain Bressendorff, Herlev Hospital
- Investigators
- Iain Bressendorff, MD PhD, Principal investigator, Herlev and Gentofte Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05897372
- Sponsor's protocol ID
- PRIMETIME - WP3
- Acronym
- WP3
- Status last verified
- Sep 2024
- First submitted
- 31 May 2023
- Last updated
- 25 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility of Aggressive Albuminuria Reduction in Biopsy-Proven Diabetic Nephropathy - a Pilot Study
- ClinicalTrials.gov ID
- NCT05897372
- Acronym / sponsor ID
- WP3 / PRIMETIME - WP3
- Conditions
- Diabetic Kidney Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Iain BressendorffUniversity, hospital or other
- Study start
- 1 Aug 2023 (actual)
- Primary completion
- 23 Sep 2024 (actual)
- Study completion
- 23 Sep 2024 (actual)
- First posted
- 9 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized, controlled, open-label, parallel-group, clinical trial.
| Arm | Type | Receives |
|---|---|---|
| Standard of Care | Active comparator | Drug: ACEi / ARB, SGLT2i, finerenone, semaglutide, pentoxifylline, hydrochlorthiazide, baricitinibMaximally tolerated dose of ACEi or ARB (but not both), SGLT2i, and finerenone. Blood pressure target <130/80 mm Hg |
| Albuminuria-reduction protocol | Experimental | Drug: ACEi / ARB, SGLT2i, finerenone, semaglutide, pentoxifylline, hydrochlorthiazide, baricitinibMaximally 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 years
- Diagnosis of diabetes mellitus type 2 (American Diabetes Association / European Association for the Study of Diabetes (ADA/EASD) definition)10
- Biopsy-proven diabetic nephropathy
- UACR ≥ 2,000 mg/g or
- UACR ≥ 1,500 mg/g if treated with sodium-glucose cotransporter 2 inhibitor (SGLT2i)
Key exclusion criteria (17 listed)
- Kidney transplant recipient
- Findings on kidney biopsy suggestive of other or concomitant glomerulonephritis (findings associated with hypertensive nephropathy are not exclusion criteria).
- Plasma potassium at baseline > 5.2 mmol/L.
- Active malignancy (basal or squamous cell skin carcinoma, localised prostate cancer, and cancer with no signs of reoccurrence after 5 years are exempt from this).
- Systolic heart failure with NYHA class III-IV.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ACEi / ARB, SGLT2i, finerenone, semaglutide, pentoxifylline, hydrochlorthiazide, baricitinibStandard of care for diabetic kidney disease. | Drug | Albuminuria-reduction protocol, Standard of Care |
Primary outcome
urine albumin/creatinin-ratio (UACR) reduction to less than 50% of baseline
Time frame: after 9 months of treatment
number of subjects achieving this endpoint
11 secondary outcomes
UACR reduction to less than 70% of baseline
Time frame: after 9 months of treatment
UACR less than 300
Time frame: after 9 months of treatment
difference in UACR
Time frame: after 9 months of treatment
difference in UACR
Time frame: after 10 months of treatment (1 month off study drugs)
difference in eGFR
Time frame: after 9 months of treatment
difference in eGFR
Time frame: after 10 months of treatment (1 month off study drugs)
difference in systolic and diastolic blood pressure
Time frame: after 9 months of treatment
difference in systolic and diastolic blood pressure
Time frame: after 10 months of treatment (1 month off study drugs)
incidence of plasma potassium >5.5 mmol/L
Time frame: after 9 months of treatment
incidence of plasma potassium >6.0 mmol/L
Time frame: after 9 months of treatment
incidence of symptomatic hypotension
Time frame: after 9 months of treatment
Results and safety
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Iain Bressendorff, MD PhD principal investigator
Herlev and Gentofte Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ACEi / ARB, SGLT2i, finerenone, semaglutide, pentoxifylline, hydrochlorthiazide, baricitinib in people with Diabetic Kidney Disease, run by Iain Bressendorff at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
urine albumin/creatinin-ratio (UACR) reduction to less than 50% of baseline (time frame: after 9 months of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2024.