Aspirin and Renal Disease Progression in Patients With Type 2 Diabetes

• Status: Unknown status
• Trial end date: 2018-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The pathophysiology of diabetes is multifactorial. Beyond genetic susceptibility loci, a lot of acquired risk factors are involved in the development and progression of the disease. Chronic complications of diabetes can be divided into vascular and nonvascular. The risk of developing complications increases with the duration of hyperglycemia, and usually become apparent in the second decade of hyperglycemia. Vascular complications are further subdivided into microvascular (retinopathy, nephropathy and neuropathy) and macrovascular (coronary artery disease, peripheral arterial disease, cerebrovascular disease). It is estimated that the annual decline of estimated glomerular filtration rate (eGFR) in diabetic adults is about 2.1-2.7 ml/min.

While there is consolidated evidence about the use of aspirin (ASA) for secondary prevention in diabetic patients, there is no consensus on the use in primary prevention; the use of ASA in these patients is at physician discretion.

ASA is an effective antithrombotic agent that inhibits the production of thromboxane (Tx) A2 and other prostaglandins by blocking cyclooxygenase (COX). In patients treated with aspirin, serum TxB₂ level is the most reliable in vivo indicator of COX-1 inhibition than TxA2, due to its short half-life and artifacts associated with platelet activation ex vivo.

COX are present in the kidney in the macula densa, in the medulla and in the interstitium. Experimental animals models have demonstrated that COX are involved in regulation of renal blood flow. In particular, in a murine animal model, after the administration of COX inhibitors such as aspirin and celecoxib, it was observed an improvement in renal plasma flow and eGFR, suggesting a role for Tx in the progression of renal damage However, data on the relationship between aspirin and renal function in humans are scarce. In a recent work lead on a large cohort of 800 patients with non-valvular atrial fibrillation, ASA use was associated with a reduced progression of eGFR <45 ml/min during 2 years of follow-up. Furthermore, basal levels of urinary excretion of TxB2, correlated inversely with the use of aspirin and with the decrease of eGFR at follow-up.

The aim of the study is to evaluate the decline in renal function in diabetic patients treated with low-dose aspirin (100 mg/day) vs. untreated diabetic patients.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Roma La Sapienza
• Treatments: Aspirin

Criteria

Inclusion Criteria:

• Diagnosis of type 2 diabetes: random blood glucose ≥ 200 mg / dl, fasting blood glucose ≥ 126 mg/dl, blood glucose 2 hours after oral glucose tolerance test (75 g) ≥200 mg/dl, treatment with glucose-lowering agents.

Exclusion Criteria:

1. History of cardiovascular or cerebrovascular events;

2. Presence of inadequate glycaemic control (glycosylated haemoglobin ≥8%);

3. Clinical diagnosis of type 1 diabetes (diagnosis of diabetes and insulin use before 35 years of age);

4. Patients with renal impairment in G4 stage (eGFR <30 ml/min) at baseline;

5. Chronic active infection or evidence of malignancy in the last 5 years;

6. Autoimmune systemic disease;

7. Cardiac arrhythmia;

8. Use of non-steroidal anti-inflammatory drugs, vitamin supplements, or other antiplatelet agents in the previous 30 days;

9. Liver Failure (eg cirrhosis);

10. Use of anticoagulants;

11. Life expectancy <1 year;

12. Known allergy to aspirin.