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Aspirin and Renal Disease Progression in Patients With Type 2 Diabetes (LEDA)

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ClinicalTrials.gov Identifier: NCT02895113
Recruitment Status : Unknown
Verified September 2016 by Francesco Violi, University of Roma La Sapienza.
Recruitment status was:  Not yet recruiting
First Posted : September 9, 2016
Last Update Posted : September 9, 2016
Sponsor:
Information provided by (Responsible Party):
Francesco Violi, University of Roma La Sapienza

Brief 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.


Condition or disease Intervention/treatment Phase
Diabetes Drug: Aspirin Other: Placebo Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 418 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Aspirin on Renal Disease Progression in Patients With Type 2 Diabetes: a Multicentre Double-blind, Placebo-controlled, Randomised Trial. The LEDA (renaL disEase Progression by Aspirin in Diabetic pAtients) Study.
Study Start Date : January 2017
Estimated Primary Completion Date : January 2018
Estimated Study Completion Date : September 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin

Arm Intervention/treatment
Experimental: Aspirin
Patients will be treated with aspirin 100 mg/day for one year
Drug: Aspirin
Patients suffering from type 2 diabetes will be randomized to receive 100 mg/day or placebo for one year
Other Names:
  • Cardioaspirin
  • Acetylsalicylic acid

Placebo Comparator: Placebo
Patients will be treated with placebo for one year
Other: Placebo
Patients in this arm will be treated with placebo




Primary Outcome Measures :
  1. Changes in renal function in diabetic patients treated with aspirin [ Time Frame: 1 year ]

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

    • The absolute change in eGFR, calculated as the difference between eGFR at 12 months - baseline eGFR;
    • The rapid decline in renal function, defined as a reduction of eGFR ≥5 ml/min at 1 years.
    • The change of renal function class (from G1 to G2, from G2 to G3a and so on) at 6 and 12 months.


Secondary Outcome Measures :
  1. Relationship between changes of Thromboxane B2 excretion and renal function in diabetic patients treated with aspirin [ Time Frame: 1 year ]
    As secondary endpoint, we will evaluate changes in the urinary excretion TxB2 both baseline and at one year. Changing levels of urinary TxB2 will then be related to renal function.



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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02895113


Contacts
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Contact: Francesco Violi, MD +390649970893 francesco.violi@uniroma1.it
Contact: Daniele Pastori, MD +390649970893 daniele.pastori@uniroma1.it

Locations
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Italy
Internal and Medical Specialities Department - Policlinico Umberto I
Rome, Italy, 00161
Sponsors and Collaborators
University of Roma La Sapienza
Investigators
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Principal Investigator: Francesco Violi, MD Sapienza University of Rome

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Francesco Violi, Full professor, University of Roma La Sapienza
ClinicalTrials.gov Identifier: NCT02895113     History of Changes
Other Study ID Numbers: LEDA study
First Posted: September 9, 2016    Key Record Dates
Last Update Posted: September 9, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Francesco Violi, University of Roma La Sapienza:
Aspirin
Diabetes
Renal function
Thromboxane
Additional relevant MeSH terms:
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Aspirin
Kidney Diseases
Diabetes Mellitus
Disease Progression
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Disease Attributes
Pathologic Processes
Urologic Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics