None listed
Conditions
Interventions
GROUP 1 Type of group
This group will be treated with Avosentan, in a dose of 25 mg, in tablets, PO, QD for 42 months.
Group name:GROUP 3 Type of group
This group will be treated with Avosentan Placebo, in tablets, PO, QD for 42 months.
Sponsors
SPEEDEL PHARMA LTD.,
Eligibility
Inclusion criteria
Inclusion criteria: 1) Male or female patients between 21 and 80 years of age. 2) Patients with type 2 diabetes mellitus diagnosed for at least 3 years and receiving oral antidiabetic treatment and / or insulin. 3) Female patients either: a) Postmenopausal for ≥ 2 years. OR b) Surgically sterile. OR c) If they are of childbearing age, that they use double contraception, with at least one method that is barrier contraception. 4) Proteinuria. 5) Patients with serum creatinine between 1.5 and 3.2 mg / dL. 6) In standard treatment for diabetic nephropathy for at least 6 months before screening. 7) That they can provide written informed consent before participating in the study.
Exclusion criteria
Exclusion criteria: 1) Patients with type 1 diabetes mellitus. 2) Patients with proteinuria of non-diabetic origin. 3) Patients with a kidney transplant. 4) Patients who have suffered a nephrectomy. 5) Patients with an estimated VFG ≤ 15 mL / min. 6) Patients with blood pressure> 160/100 mmHg with or without antihypertensive medication 7) Patients with glycosylated hemoglobin (HbA1c)> 12%. 8) Patients with normal sinus rhythm, no pacemaker, who do not take antiarrhythmic drugs and who do not have a complete branch block, but who have an absolute increase in QT or absolute QTc> 500 msec. 9) Patients with recent percutaneous transluminal coronary angioplasty, percutaneous coronary intervention, coronary artery bypass graft, or any other major surgery. 10) Patients with recent acute myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack. 11) Patients with congestive heart failure grade III or IV. 12) Patients with arrhythmias that endanger life. 13) Patients who test positive for hepatitis B surface antigen or hepatitis C antibody to Visit 1 and who have abnormal liver function. 14) Patients who have received treatment with an endothelin receptor antagonist in the 3 months prior to selection. 15) Patients who are being treated with spironolactone or eplerenone at study entry. 16) Patients treated with amiodarone in the 4 weeks prior to study entry. 17) Women of childbearing age who are not using an adequate contraceptive method. 18) Pregnant women or breastfeeding. 19) Patients with a neoplasm that is considered to live <12 months. 20) Patients with a history of alcoholism and / or drug addiction. 21) Patients with a known history of an important psychiatric condition that could interfere with the conduct of the study. 22) Patients with endocarditis and / or acute pericarditis. 23) Patients allergic to avosentan or to any other endothelin receptor antagonist. 24) Patients who participated in another clinical study or who have donated blood within 60 days of their random assignment to this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Serum creatinine: In peripheral blood samples along with the rest of biochemical analytes. End-stage renal disease: When the glomerular filtration rate (GFR) ≤ 15 ml / min, using the albumin / creatinine index. Evaluation of the number of patients who die. Measure:Time to reach the composite endpoint: doubling of serum creatinine, end-stage renal disease or death. Timepoints:When the event is presented. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:1) Clinical evaluation to determine the time and the proportion of patients in whom the diagnosis of ESRD and death was reached. In addition to determining the time in which the serum creatinine was doubled. 2) Clinical evaluation to determine the time in which the patients suffered from: a) Coronary or peripheral vascular revascularization, not including amputations. OR b) Acute non-fatal myocardial infarction. OR c) Stroke. OR d) Congestive heart failure. OR e) Unstable angina. OR f) Cardiovascular death. 3) Clinical determination of VFG and creatinine clearance, based on serum creatinine values ​​(calculated) and that obtained in a laboratorial determination of collected urine. Likewise, the variation of these from the baseline will be determined. 4) Clinical evaluation to determine the time in which death was reached, due to cardiovascular or non-cardiovascular causes 7) Time to cardiovascular mortality. 8) Time to non-cardiovascular mortality. Measure:Other endpoints: 1) Time to ERCT or death. 2) Proportion of patients with the composite criterion of primary assessment. 3) Time to each of the three compounds of the composite primary assessment criterion. 4) Time to each of the six compounds of the composite criterion of cardiac assessment. 5) Index of change from the baseline in the glomerular filtration rate (GFR) calculated. 6) Rate of change from baseline in creatinine clearance. 7) Time to cardiovascular mortality. 8) Time to non-cardiovascular mortality. 9) Index of change from the baseline in the variation of VFG. 10) Rate of change from baseline in the variation of creatinine clearance. Timepoints:The clinical evaluation for the different variables will be performed when an event occurs. Measurement of creatinine and the determination of calculated VEG and creatinine clearance: Week 0 and months 1, 3, 6, 14, 20, 26, 30, 36 and 42. Direct VFG: Week 0 and month 24, 25, 41 and 42. ; Outcome | — |
Countries
Czech Republic, Estonia, Finland, Hungary, Italy, Latovia, Latvia, Sweden, United Kindgdom
Outcome results
None listed