Kidney Injury, Proteinuria, Hypertension
Conditions
Keywords
Kidney Injury, Proteinuria, Hypertension, Anti-VEGF
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).
Interventions
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).
DRUGPlacebo oral tablet
Placebo will be given daily and will be doubled after 4 weeks of start of therapy.
Sponsors
National Kidney Foundation, United States
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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 |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Improvement in Estimated Glomerular Filtration Rate (eGFR) ≥25% From Before Enrollment | Baseline, Month 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 1 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Isosorbide Mononitrate Isosorbide Mononitrate: 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). | 7 |
| Placebo Placebo oral tablet: Placebo will be given daily and will be doubled after 4 weeks of start of therapy. | 2 |
| Total | 9 |
Baseline characteristics
| Characteristic | Placebo | Total | Isosorbide Mononitrate |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 9 Participants | 7 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 2 Participants | 9 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 2 |
| other Total, other adverse events | 2 / 7 | 0 / 2 |
| serious Total, serious adverse events | 0 / 7 | 0 / 2 |
Outcome results
Primary
Number of Participants With a Reduction in UPC of > 500 mg/Day From That Measured Before Enrollment
Time frame: Baseline, Month 2
Population: Data were not collected for 2 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | Number of Participants With a Reduction in UPC of > 500 mg/Day From That Measured Before Enrollment | 1 Participants |
| Placebo | Number of Participants With a Reduction in UPC of > 500 mg/Day From That Measured Before Enrollment | 0 Participants |
Primary
Number of Participants With a Reduction in UPC of > 500 mg/Day From That Measured Before Enrollment
Time frame: Baseline, Month 3
Population: Data were not collected for 2 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | Number of Participants With a Reduction in UPC of > 500 mg/Day From That Measured Before Enrollment | 3 Participants |
| Placebo | Number of Participants With a Reduction in UPC of > 500 mg/Day From That Measured Before Enrollment | 1 Participants |
Primary
Number of Participants With a Reduction in Urine Protein Creatinine Ratio (UPC) of > 500 mg/Day From That Measured Before Enrollment
Time frame: Baseline, Month 1
Population: Data were not collected for 2 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | Number of Participants With a Reduction in Urine Protein Creatinine Ratio (UPC) of > 500 mg/Day From That Measured Before Enrollment | 1 Participants |
| Placebo | Number of Participants With a Reduction in Urine Protein Creatinine Ratio (UPC) of > 500 mg/Day From That Measured Before Enrollment | 0 Participants |
Secondary
Number of Participants With Improvement in Estimated Glomerular Filtration Rate (eGFR) ≥25% From Before Enrollment
Time frame: Baseline, Month 3
Population: Data were not collected for 2 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | Number of Participants With Improvement in Estimated Glomerular Filtration Rate (eGFR) ≥25% From Before Enrollment | 1 Participants |
| Placebo | Number of Participants With Improvement in Estimated Glomerular Filtration Rate (eGFR) ≥25% From Before Enrollment | 0 Participants |
Secondary
Number of Participants With Improvement in Estimated Glomerular Filtration Rate (eGFR) ≥25% From Before Enrollment
Time frame: Baseline, Month 1
Population: Data were not collected for 2 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | Number of Participants With Improvement in Estimated Glomerular Filtration Rate (eGFR) ≥25% From Before Enrollment | 0 Participants |
| Placebo | Number of Participants With Improvement in Estimated Glomerular Filtration Rate (eGFR) ≥25% From Before Enrollment | 0 Participants |
Secondary
Number of Participants With Improvement in Estimated Glomerular Filtration Rate (eGFR) ≥25% From Before Enrollment
Time frame: Baseline, Month 2
Population: Data were not collected for 2 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | Number of Participants With Improvement in Estimated Glomerular Filtration Rate (eGFR) ≥25% From Before Enrollment | 0 Participants |
| Placebo | Number of Participants With Improvement in Estimated Glomerular Filtration Rate (eGFR) ≥25% From Before Enrollment | 0 Participants |
Secondary
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
Time frame: Baseline, Week 7
Population: Data were not collected for 3 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | 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 | 3 Participants |
| Placebo | 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 | 2 Participants |
Secondary
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
Time frame: Baseline, Week 8
Population: Data were not collected for 2 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | 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 | 3 Participants |
| Placebo | 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 | 2 Participants |
Secondary
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
Time frame: Baseline, Week 11
Population: Data were not collected for 3 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | 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 | 3 Participants |
| Placebo | 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 | 2 Participants |
Secondary
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
Time frame: Baseline, Week 12
Population: Data were not collected for 2 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | 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 | 3 Participants |
| Placebo | 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 | 2 Participants |
Secondary
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
Time frame: Baseline, Week 9
Population: Data were not collected for 3 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | 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 | 3 Participants |
| Placebo | 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 | 2 Participants |
Secondary
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
Time frame: Baseline, Week 2
Population: Data were not collected for 3 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | 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 | 2 Participants |
| Placebo | 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 | 1 Participants |
Secondary
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
Time frame: Baseline, Week 10
Population: Data were not collected for 3 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | 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 | 2 Participants |
| Placebo | 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 | 2 Participants |
Secondary
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
Time frame: Baseline, Week 1
Population: Data were not collected for 3 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | 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 | 0 Participants |
| Placebo | 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 | 1 Participants |
Secondary
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
Time frame: Baseline, Week 3
Population: Data were not collected for 3 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | 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 | 3 Participants |
| Placebo | 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 | 1 Participants |
Secondary
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
Time frame: Baseline, Week 4
Population: Data were not collected for 2 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | 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 | 4 Participants |
| Placebo | 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 | 2 Participants |
Secondary
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
Time frame: Baseline, Week 5
Population: Data were not collected for 3 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | 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 | 2 Participants |
| Placebo | 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 | 1 Participants |
Secondary
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
Time frame: Baseline, Week 6
Population: Data were not collected for 3 in the Isosorbide Mononitrate arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Isosorbide Mononitrate | 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 | 3 Participants |
| Placebo | 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 | 2 Participants |