Feasibility of Aggressive Albuminuria Reduction in Biopsy-Proven Diabetic Nephropathy - a Pilot Study

NCT05897372 | Terminated Phase 2

• 1 other identifier: PRIMETIME - WP3
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Diabetic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• urine albumin/creatinin-ratio (UACR) reduction to less than 50% of baseline

  number of subjects achieving this endpoint

  after 9 months of treatment

Secondary Outcomes (11)

• UACR reduction to less than 70% of baseline

  after 9 months of treatment

• UACR less than 300

  after 9 months of treatment

• difference in UACR

  after 9 months of treatment

• difference in UACR

  after 10 months of treatment (1 month off study drugs)

• difference in eGFR

  after 9 months of treatment

Study Arms (2)

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

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.

Drug: ACEi / ARB, SGLT2i, finerenone, semaglutide, pentoxifylline, hydrochlorthiazide, baricitinib

Interventions

ACEi / ARB, SGLT2i, finerenone, semaglutide, pentoxifylline, hydrochlorthiazide, baricitinib DRUG

Standard of care for diabetic kidney disease.

Albuminuria-reduction protocol; Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Kidney transplant recipient
• 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.
• 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.

Sponsors & Collaborators

• Iain Bressendorff: lead

Study Sites (1)

Department of Nephrology, Herlev and Gentofte Hospital

Herlev, 2730, Denmark

Location

MeSH Terms

Conditions

Diabetic Nephropathies

Interventions

Angiotensin-Converting Enzyme Inhibitors; finerenone; semaglutide; Pentoxifylline; baricitinib

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Theobromine; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Iain Bressendorff, MD PhD

  Herlev and Gentofte Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD PhD, Principal Investigator

Model Details: Randomized, controlled, open-label, parallel-group, clinical trial.

Study Record Dates

• First Submitted: May 31, 2023
• First Posted: June 9, 2023
• Study Start: August 1, 2023
• Primary Completion: September 23, 2024
• Study Completion: September 23, 2024
• Last Updated: September 25, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)