NCT04794517

Dapagliflozin in Non-diabetic Stage IV CKD

Evaluating the Short-term Renal and Systemic Effects of Dapagliflozin in Non-diabetic Patients With Stage IV CKD at Risk of ESKD Because of Severe Renal Insufficiency and Persistent Proteinuria

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: Mario Negri Institute for Pharmacological Research · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a phase 2b, prospective, randomized, cross-over, double-blind, placebo-controlled trial primarily aimed at assessing whether the SGLT2 inhibitor dapagliflozin ameliorates hyperfiltration and reduces proteinuria as compared to placebo in patients with non-diabetic CKD, with particular focus on those at highest risk of progression to end stage kidney disease (ESKD) because of severe renal insufficiency (Stage IV CKD) and proteinuria (\>0.5 g/24 hours). The study will also evaluate renal and systemic mechanisms mediating treatment effects on GFR and will explore biochemical factors possibly mediating these effects.

Detailed description

As chronic kidney disease (CKD) continues to increase worldwide, along with the demand for related life-saving therapies, the financial burden of CKD will place an increasing drain on health care systems. Experimental studies showed that glomerular capillary hypertension and impaired sieving function with consequent protein overload play a pathogenic role in the progression of CKD. Consistently, human studies show that proteinuria is an independent predictor of progression and that its reduction is renoprotective. At comparable BP control, inhibitors of the renin-angiotensin system (RAS), including angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), more effectively than non-RAS inhibitor therapy reduce proteinuria, slow progression to ESRD, and even improve the kidney function achieving disease regression in some cases. In participants with diabetes, RAS inhibitors delay the onset of microalbuminuria and its progression to macroalbuminuria, and ACE inhibitors may reduce the excess cardiovascular mortality associated with diabetic renal disease. In addition to RAS inhibitors, however, multimodal approaches including lifestyle modifications and multidrug therapy will be required in most cases to optimize control of the several risk factors for CKD and related cardiovascular morbidity. Novel medications, including proximal tubular sodium - glucose co-transporter -2 (SGLT2 inhibitors - that ameliorate glomerular hyperfiltration and proteinuria and slow renal disease progression in type 2 diabetes by mechanisms apparently independent of improved metabolic control - might help further improve the cost-effectiveness of renoprotective interventions even in non-diabetic CKD. This phase 2, prospective, randomized, cross over, placebo-controlled trial will primarily aim to assess whether the SGLT2 inhibitor dapagliflozin ameliorates hyperfiltration and reduces proteinuria as compared to placebo in patients with non-diabetic CKD, with particular focus on those at highest risk of progression to end stage kidney disease (ESKD) because of severe renal insufficiency (Stage IV CKD) and proteinuria (\>0.5 g/24 hours).

Conditions

• Chronic Kidney Diseases

Interventions

Type	Name	Description
DRUG	Dapagliflozin 10Mg Tab	Dapagliflozin 10 mg/die will be administered orally for six-weeks.
OTHER	Placebo	Placebo one tablet/die will be administered orally for six-weeks.

Timeline

• Start date: 2021-11-08
• Primary completion: 2024-05-07
• Completion: 2024-05-07
• First posted: 2021-03-12
• Last updated: 2024-05-10

Locations

1 site across 1 country: Italy