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Bosentan Use in Patients With Diabetic Nephropathy

Primary Purpose

Type 2 Diabetes

Status

Terminated

Phase

Phase 3

Locations

Canada

Study Type

Interventional

Intervention

bosentan

About this trial

This is an interventional treatment trial for Type 2 Diabetes

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Men or women ≥ 18 years of age with a body weight of ≥ 40 kg;
For female patients, only non-pregnant women who are surgically sterile, postmenopausal or have documented infertility (over 50 years of age and amenorrheic for at least 1 year), or those of childbearing potential using intrauterine devices (IUDs);
Patients diagnosed Type 2 diabetes with overt nephropathy (urinary albumin excretion ≥ 300mg/24h);
Patients on current treatment with angiotensin II receptor blockers for ≥ 3 months;
Patients stable for at least 3 months prior to screening (no change in medications for diabetic nephropathy);
Provide written informed consent;

Exclusion Criteria:

Patients with a history of pulmonary chronic obstructive disease, cardiac failure or coronary artery disease;
Patients with documented cancers, acute infections or chronic inflammatory diseases;
Patients who are pregnant or breast-feeding;
Patients with known hepatic disorders or AST and ∕or ALT upper than normal limit;
Patients with hemoglobin or hematocrit that is ≥ 30% below the normal range (patients with secondary polycythemia are permitted);
Patients with systolic blood pressure < 110mm Hg;
Patients with plasmatic albumin level < 30g/L;
Patients with a documented creatinine clearance ≤ 60ml/min;
Patients on anticoagulants or anti-inflammatory drugs, including cyclooxygenase inhibitors, AINS, prednisone and immunosuppressive drugs, platelet aggregation inhibitors, except low dose aspirin, ACE inhibitors, antidiabetic agents (rosiglitazone, pioglitazone) and antioxidants (vitamin E)(except statins or low-dose aspirin ≤ 80mg/day);
Patients on treatment or planned treatment with another investigational drug;
Patients who are receiving an endothelin receptor antagonist, phosphodiesterase type 5 inhibitor, or with a prostanoid (excluding acute administration during a catheterization procedure to test vascular reactivity) within 2 months of inclusion;
Patients who are receiving calcineurin-inhibitors (i.e., cyclosporine A and tacrolimus), fluconazole, glibenclamide (glyburide) at inclusion or are expected to receive any of these drugs during the study;
Patients with a known hypersensitivity to bosentan or any of the excipients;

Sites / Locations

CHUM

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

Bosentan 62.5mg bid x4 weeks; up-titrated to 125mg bid x12 weeks;

placebo given bid same as experimental arm;

Outcomes

Primary Outcome Measures

change from baseline to week 16 in renal inflammation. The following urinary inflammatory/oxidative stress parameters will be measured: - TNF

Secondary Outcome Measures

change from baseline to week 16 in renal functioning. The following renal function parameter will be measured: - 24h UAE;

Full Information

NCT ID

NCT00638131

First Posted

March 12, 2008

Last Updated

July 22, 2020

Sponsor

Centre hospitalier de l'Université de Montréal (CHUM)

Collaborators

Actelion

1. Study Identification

Unique Protocol Identification Number

NCT00638131

Brief Title

Bosentan Use in Patients With Diabetic Nephropathy

Official Title

Effect of Bosentan on Systemic and Renal Inflammatory Markers in Patients With Diabetic Nephropathy on Angiotensin II Receptor Blockers

Study Type

Interventional

2. Study Status

Record Verification Date

June 2010

Overall Recruitment Status

Terminated

Why Stopped

problem of recruitment

Study Start Date

January 2009 (undefined)

Primary Completion Date

March 2010 (Actual)

Study Completion Date

June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Centre hospitalier de l'Université de Montréal (CHUM)

Collaborators

Actelion

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

There is little doubt of the necessity for further improvement in the prevention and therapy of end-stage renal disease. Despite the success of ARB in treating diabetic nephropathy, not all patients obtain satisfactory control of blood pressure, albuminuria and decline in renal function. Experimental data have provided us with a rationale for the potential added benefits of ET receptor blockade to the AII inhibition in diabetic renal protection. Considering the nephroprotective effect of bosentan in diabetic rats, clinical studies are warranted to assess whether ET receptor antagonism has additive renoprotective effects on top of AII inhibition.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Bosentan 62.5mg bid x4 weeks; up-titrated to 125mg bid x12 weeks;

Arm Title

Arm Type

Placebo Comparator

Arm Description

placebo given bid same as experimental arm;

Intervention Type

Drug

Intervention Name(s)

bosentan

Other Intervention Name(s)

Tracleer

Intervention Description

62.5mg bid x4 weeks, up-titrate to 125mg bid x12 weeks

Primary Outcome Measure Information:

Title

change from baseline to week 16 in renal inflammation. The following urinary inflammatory/oxidative stress parameters will be measured: - TNF

Time Frame

16 weeks

Secondary Outcome Measure Information:

Title

change from baseline to week 16 in renal functioning. The following renal function parameter will be measured: - 24h UAE;

Time Frame

16 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Men or women ≥ 18 years of age with a body weight of ≥ 40 kg; For female patients, only non-pregnant women who are surgically sterile, postmenopausal or have documented infertility (over 50 years of age and amenorrheic for at least 1 year), or those of childbearing potential using intrauterine devices (IUDs); Patients diagnosed Type 2 diabetes with overt nephropathy (urinary albumin excretion ≥ 300mg/24h); Patients on current treatment with angiotensin II receptor blockers for ≥ 3 months; Patients stable for at least 3 months prior to screening (no change in medications for diabetic nephropathy); Provide written informed consent; Exclusion Criteria: Patients with a history of pulmonary chronic obstructive disease, cardiac failure or coronary artery disease; Patients with documented cancers, acute infections or chronic inflammatory diseases; Patients who are pregnant or breast-feeding; Patients with known hepatic disorders or AST and ∕or ALT upper than normal limit; Patients with hemoglobin or hematocrit that is ≥ 30% below the normal range (patients with secondary polycythemia are permitted); Patients with systolic blood pressure < 110mm Hg; Patients with plasmatic albumin level < 30g/L; Patients with a documented creatinine clearance ≤ 60ml/min; Patients on anticoagulants or anti-inflammatory drugs, including cyclooxygenase inhibitors, AINS, prednisone and immunosuppressive drugs, platelet aggregation inhibitors, except low dose aspirin, ACE inhibitors, antidiabetic agents (rosiglitazone, pioglitazone) and antioxidants (vitamin E)(except statins or low-dose aspirin ≤ 80mg/day); Patients on treatment or planned treatment with another investigational drug; Patients who are receiving an endothelin receptor antagonist, phosphodiesterase type 5 inhibitor, or with a prostanoid (excluding acute administration during a catheterization procedure to test vascular reactivity) within 2 months of inclusion; Patients who are receiving calcineurin-inhibitors (i.e., cyclosporine A and tacrolimus), fluconazole, glibenclamide (glyburide) at inclusion or are expected to receive any of these drugs during the study; Patients with a known hypersensitivity to bosentan or any of the excipients;

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Maryse Courteau, MD

Organizational Affiliation

CHUM

Official's Role

Principal Investigator

Facility Information:

Facility Name

CHUM

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H2L 4M1

Country

Canada

12. IPD Sharing Statement

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Bosentan Use in Patients With Diabetic Nephropathy

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