Isosorbide Mononitrate For Anti-Vascular Endothelial Growth Factor (VEGF) Induced Kidney Injury

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to test the hypothesis that isosorbide mononitrate prevents deterioration of renal function in patients receiving anti-angiogenic therapies that target vascular endothelial growth factor (VEGF).

Official Title
-----------------
Isosorbide Mononitrate For Anti-Vascular Endothelial Growth Factor (VEGF) Induced Kidney Injury

Conditions
-----------------
Kidney Injury, Proteinuria, Hypertension

Intervention / Treatment
-----------------
* Drug: Isosorbide Mononitrate
* Drug: Placebo oral tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients on or enrolled for anti-VEGF therapy new-onset proteinuria, defined as a urine protein: creatinine ratio (UPC) of >500mg/g or hypertension (Systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg) or a decrease in eGFR by ≥ 25% from baseline before starting therapy. Exclusion Criteria: Pregnant women Breast-feeding women.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Isosorbide Mononitrate<br> | Drug: Isosorbide Mononitrate<br>* The starting dose will be Isosorbide Mononitrate 60 mg ER daily and after 4 weeks, if tolerated but response is not achieved, the dose will be escalated to Isosorbide Mononitrate 120 mg ER daily (2 tabs of 60 mg ER tablets).<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo oral tablet<br>* Placebo will be given daily and will be doubled after 4 weeks of start of therapy.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Reduction in Urine Protein Creatinine Ratio (UPC) of > 500 mg/Day From That Measured Before Enrollment |  | Baseline, Month 1 | 
| Number of Participants With a Reduction in UPC of > 500 mg/Day From That Measured Before Enrollment |  | Baseline, Month 2 | 
| Number of Participants With a Reduction in UPC of > 500 mg/Day From That Measured Before Enrollment |  | Baseline, Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Improvement in Estimated Glomerular Filtration Rate (eGFR) ≥25% From Before Enrollment |  | Baseline, Month 1 | 
| Number of Participants With Improvement in Estimated Glomerular Filtration Rate (eGFR) ≥25% From Before Enrollment |  | Baseline, Month 2 | 
| Number of Participants With Improvement in Estimated Glomerular Filtration Rate (eGFR) ≥25% From Before Enrollment |  | Baseline, Month 3 | 
| Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment |  | Baseline, Week 1 | 
| Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment |  | Baseline, Week 2 | 
| Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment |  | Baseline, Week 3 | 
| Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment |  | Baseline, Week 4 | 
| Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment |  | Baseline, Week 5 | 
| Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment |  | Baseline, Week 6 | 
| Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment |  | Baseline, Week 7 | 
| Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment |  | Baseline, Week 8 | 
| Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment |  | Baseline, Week 9 | 
| Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment |  | Baseline, Week 10 | 
| Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment |  | Baseline, Week 11 | 
| Number of Participants With Reduction in Systolic Blood Pressure (SBP) of ≥ 10 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 5 mm Hg From Before Enrollment |  | Baseline, Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Proteinuria, Kidney Injury, Hypertension, Anti-VEGF