TreatIng Microalbuminuria Over 24 Weeks in Subjects With or Without Type 2 Diabetes or HYpertension

NCT05268926 | Terminated Phase 2 DMC

• 2 other identifiers: 2021/10012021-004073-31
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Increased albuminuria has a relatively high prevalence in the general population (5-9%) People with increased albuminuria are more likely to develop progressive kidney and cardiovascular disease compared to persons with no albuminuria. ACE-inhibitors or Angiotensin Receptor Blockers are recommended by clinical practice guidelines to lower albuminuria in patients with hypertension and diabetes. However, despite these drugs decrease albuminuria by approximately 30%, elevated albuminuria remains present in the substantial proportion of persons in the general population. SGLT2 inhibitors are a relatively new class of drugs. Originally they were developed as oral antihyperglycemic drugs. SGLT2 inhibitors have been demonstrated to lower albuminuria and protect the kidney in patients with established chronic kidney disease (CKD) with or without diabetes. Whether the efficacy of SGTL2 inhibitors to lower albuminuria (and possibly confer kidney protection) to persons in the general population (with or without diabetes or hypertension) with persistent albuminuria who generally are at early stages of CKD is unknown. Objective: To assess the albuminuria lowering effects of dapagliflozin in subjects with and without diabetes or hypertension and persistent elevated albuminuria. Study design: Randomized placebo-controlled double blind clinical trial of 24 weeks in duration followed by a 4 weeks wash-out period

Conditions

Albuminuria

Outcome Measures

Primary Outcomes (1)

• urinary albumin/creatinine ratio

  Change in albuminuria defined as urinary albumin/creatinine ratio: UACR) with dapagliflozin 10mg/d for 24 weeks relative to placebo

  24 weeks

Secondary Outcomes (6)

• systolic and diastolic blood pressure

  24 weeks

• body weight

  24 weeks

• HbA1c

  24 weeks

• eGFR

  24 weeks

• change in UACR

  24 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Dapagliflozin 10mg/day

ACTIVE COMPARATOR

Drug: Dapagliflozin 10Mg Tab

Interventions

Dapagliflozin 10Mg Tab DRUG

dapagliflozin 10 mg/d or matched placebo

Dapagliflozin 10mg/day

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 45 to 80 years
• Persistent urinary albumin:creatinine ratio (UACR) ≥ 2.5 mg/mmol (\~25 mg/g)
• Willing to sign informed consent

You may not qualify if:

• Diagnosis of type 1 diabetes mellitus
• eGFR \< 25 ml/min/1.73m2
• UACR \> 3500 mg/g
• Concurrent treatment with SGLT2 inhibitor
• Receiving immunosuppressive therapy within 6 months prior to enrolment
• History of diabetic ketoacidosis
• Active malignancy aside from treated squamous cell or basal cell carcinoma of the skin.
• Initiation or changes in the dose of interventions in the renin-angiotensinaldosterone- system, diuretics, GLP-1 receptor agonists within 6 weeks of screening will not be allowed.
• Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following:
• History of active inflammatory bowel disease within the last six months;
• Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
• Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months;
• Pancreatic injury or pancreatitis within the last six months;
• Evidence of hepatic disease as determined by any one of the following: ALT or AST values exceeding 3x ULN at the screening visit, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt;
• Evidence of urinary obstruction or difficulty in voiding at screening

Sponsors & Collaborators

• University Medical Center Groningen: lead
• AstraZeneca: collaborator

Study Sites (1)

UMCG

Groningen, Netherlands

Location

MeSH Terms

Conditions

Albuminuria

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Proteinuria; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2021
• First Posted: March 7, 2022
• Study Start: February 3, 2022
• Primary Completion: February 2, 2023
• Study Completion: February 2, 2023
• Last Updated: April 17, 2024

Record last verified: 2024-04

Locations

NL (1)