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

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).

Study Overview

• Status: Terminated
• Conditions: Hypertension; Proteinuria; Kidney Injury
• Intervention / Treatment: Drug: Isosorbide Mononitrate; Drug: Placebo oral tablet

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo oral tablet; Placebo will be given daily and will be doubled after 4 weeks of start of therapy.
EXPERIMENTAL: Isosorbide Mononitrate	Drug: 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).

What is the study measuring?

Primary Outcome Measures

Outcome 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
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	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

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: National Kidney Foundation
• Investigators: Principal Investigator: Jaya Kala, MD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 26, 2019
• Primary Completion (ACTUAL): February 12, 2021
• Study Completion (ACTUAL): February 12, 2021

Study Registration Dates

• First Submitted: August 7, 2019
• First Submitted That Met QC Criteria: August 7, 2019
• First Posted (ACTUAL): August 9, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Hypertension; Proteinuria; Anti-VEGF; Kidney Injury
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Urological Manifestations; Urination Disorders; Hypertension; Wounds and Injuries; Proteinuria; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Nitric Oxide Donors; Isosorbide; Isosorbide Dinitrate; Isosorbide-5-mononitrate
• Other Study ID Numbers: HSC-MS-19-0429

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No