Renal Artery Obstruction, Hypertension, Renovascular, Ischemia Reperfusion Injury
Conditions
Keywords
elamipretide
Brief summary
This was a Phase 2a prospective, single center, randomized, double-blind, placebo-controlled study designed to assess the efficacy, pharmacokinetics, safety and tolerability of IV elamipretide for reduction of reperfusion injury in subjects with Atherosclerotic Renal Artery Stenosis (ARAS), who are undergoing percutaneous transluminal angioplasty of the renal artery (PTRA).
Detailed description
This was a Phase 2a prospective, single center, randomized, double-blind, placebo-controlled study designed to assess the efficacy, pharmacokinetics, safety and tolerability of IV elamipretide for reduction of reperfusion injury in subjects with ARAS, who are undergoing percutaneous transluminal angioplasty of the renal artery (PTRA). The randomization (1:1 active:placebo) was stratified by a diagnosis of diabetes mellitus. Participants received either 0.05 mg/kg/h elamipretide or matching placebo, administered as an IV infusion at 60 mL/h infused 30 minutes before and continued 3 hours after PTRA of the renal artery. After completion of the PTRA and stenting, subjects were to receive standard treatment.
Interventions
DRUGBendavia
DRUGPlacebo
Sponsors
Stealth BioTherapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* ≥40 and ≤80 years old. * Patients with hypertension (systolic blood pressure \[BP\] \>155 mm Hg) and/or requiring 2 or more antihypertensive medications: no restrictions will be placed on antihypertensive agents, although loop diuretics will be temporarily changed to diluting site agents (eg, hydrochlorothiazide, indapamide, metolazone) prior to each blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) study performed during the trial, unless, in the judgment of the Investigator, the change represents a hazard to the patient. ARAS patients will be identified based upon radiologic and clinical criteria suggestive of renovascular hypertension and/or hemodynamically significant renovascular disease \>60% lumen occlusion (determined by quantitative computed tomography angiography or Doppler ultrasound velocity \>200 cm/sec). * Have an estimated glomerular filtration rate of ≥15 ml/min/1.73 m2 calculated using the Modification of Diet in Renal Disease (MDRD) formula. * Have no contraindications to angiography such as severe contrast allergy. * Have no contraindications to non-contrast magnetic resonance evaluations such as a pacemaker or magnetically active metal fragments. * Able to comply with protocol. * Women of childbearing age must: * Have a negative pregnancy serum human chorionic gonadotropin test prior to receiving study drug. * Agree to use two forms of contraception for 3 months following receipt of the study drug. * Men who are sexually active and able to father a child, must agree to use one of the birth control methods listed below for the entire study and for at least 2 months after receiving the study drug: * Barrier methods (such as a condom or diaphragm) used with a spermicide. * Hormonal methods used by his partner, such as birth control pills, patches, injections, vaginal ring, or implants. * Intrauterine device (IUD) used by his partner. * Abstinence (no sex). * Competent and able to provide written informed consent
Exclusion criteria
* Advanced chronic kidney disease defined as either Stage 5 or end-stage renal disease requiring dialysis. * Have other clinically significant abnormalities or laboratory results that would, in the opinion of the investigators, compromise the safety of the patient including evidence of diabetic ketoacidosis, paraproteinemia, or triglycerides above 600 mg/dL. * Clinically significant medical conditions within the six months before administration of Bendavia (e.g., cancer, stroke, myocardial infarction, active angina, congestive heart failure) that would, in the opinion of the investigators, compromise the safety of the patient. * Have received an investigational drug within thirty (30) days of baseline. * Have a serum sodium \<135 mmol/L on the day of, and prior to, the PTRA. * Are pregnant or breast feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Glomerular Filtration Rate (GFR), as Measured by Iothalamate Clearance, at Baseline (Pre-percutaneous Renal Artery Angioplasty and 8 Weeks Post-PTRA. | Baseline (pre-PTRA) and 8 weeks post-PTRA | Change in mean glomerular filtration rate (GFR), as measured by iothalamate clearance, from baseline (pre-percutaneous renal artery angioplasty, or pre-PTRA) and 8 weeks post-PTRA.. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Regional Perfusion as Measured by MDCT at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Baseline (pre-PTRA) and 8 weeks post-PTRA | Change in mean regional perfusion as measured by Multi-Detector Computed Tomography (MDCT) Baseline (pre-PTRA) and 8 weeks post-PTRA for stented quantifiable scanned kidneys. |
| Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Baseline (pre-PTRA) and 8 weeks post-PTRA | Change in mean renal blood flow (ml/minute) as measured using Multi-Detector Computed Tomography (MDCT) at Baseline (pre-PTRA) and 8 weeks post-PTRA for stented quantifiable scanned kidneys |
| Change in Mean Renal Volume as Measured by Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Baseline (Pre-PTRA) and 8 (+4) weeks post-PTRA | Change in mean renal volume as measured by Multi-Detector Computed Tomography (MDCT) at Baseline (pre-PTRA) and 8 weeks post-PTRA. |
| Change in Mean Glomerular Flow Rate as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Baseline (pre-PTRA) and 8 weeks post-PTRA | Change in mean glomerular flow rate as measured using Multi-Detector Computed Tomography (MDCT) at baseline (pre-PTRA) and 8 weeks post-PTRA, stented quantifiable scanned kidneys. |
| Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | 27H post PTRA and 8 weeks Post PTRA | Mean change in renal oxygenation, coronal aspect, in stented kidneys between baseline (pre-PTRA) and 27 hours post-PTRA or 8 weeks post-PTRA, as measured by calculation of fractional hypoxia using blood oxygenation level-dependent magnetic resonance (BOLD-MR) imaging, with and without Bendavia |
| Mean Change in Systolic Blood Pressure Values (mmHg) From Pre-PTRA, Immediately Post-PTRA, 27 Hours and 8 (+4) Weeks Post-PTRA | Pre-PTRA and 27 hours post-PTRA and 8 weeks post-PTRA | — |
| Mean Change in Diastolic Blood Pressure | Pre-PTRA, immediately post-PTRA, 27 hours post-PTRA and 8 weeks post-PTRA | Mean Change in Diastolic Blood Pressure (DBP) values (mmHg) from baseline (pre-PTRA), immediately post-PTRA, 27 hours and 8 weeks post-PTRA, with and without Bendavia. |
| Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | Baseline (Pre-PTRA) , 27 hours post-PTRA and 8 weeks post-PTRA | Mean change in renal oxygenation, axial aspect, in stented kidneys between baseline (pre-PTRA), and 27 hours post-PTRA and 8 weeks post-PTRA as measured by calculation of fractional hypoxia using blood oxygenation level-dependent magnetic resonance (BOLD-MR) imaging. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bendavia Bendavia, intravenous infusion, 0.05 mg/kg/hr for a maximum duration of 4 hours. | 7 |
| Placebo Placebo (no active drug), intravenous infusion, for a maximum duration of 4 hours. | 9 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
Baseline characteristics
| Characteristic | Bendavia | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 66.1 years STANDARD_DEVIATION 6.41 | 72.6 years STANDARD_DEVIATION 7.78 | 69.8 years STANDARD_DEVIATION 7.72 |
| Diabetes Mellitus Status Negative | 7 Participants | 6 Participants | 13 Participants |
| Diabetes Mellitus Status Positive | 0 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 9 |
| other Total, other adverse events | 2 / 7 | 5 / 9 |
| serious Total, serious adverse events | 1 / 7 | 1 / 9 |
Outcome results
Primary
Change in Mean Glomerular Filtration Rate (GFR), as Measured by Iothalamate Clearance, at Baseline (Pre-percutaneous Renal Artery Angioplasty and 8 Weeks Post-PTRA.
Change in mean glomerular filtration rate (GFR), as measured by iothalamate clearance, from baseline (pre-percutaneous renal artery angioplasty, or pre-PTRA) and 8 weeks post-PTRA..
Time frame: Baseline (pre-PTRA) and 8 weeks post-PTRA
Population: All participants for whom GFR by iothalamate clearance was measured at Baseline (pre-PTRA) and 8 weeks post-PTRA.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bendavia | Change in Mean Glomerular Filtration Rate (GFR), as Measured by Iothalamate Clearance, at Baseline (Pre-percutaneous Renal Artery Angioplasty and 8 Weeks Post-PTRA. | 6.3 mL/min | Standard Deviation 12.14 |
| Placebo | Change in Mean Glomerular Filtration Rate (GFR), as Measured by Iothalamate Clearance, at Baseline (Pre-percutaneous Renal Artery Angioplasty and 8 Weeks Post-PTRA. | 12.0 mL/min | Standard Deviation 23.84 |
Secondary
Change in Mean Glomerular Flow Rate as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA.
Change in mean glomerular flow rate as measured using Multi-Detector Computed Tomography (MDCT) at baseline (pre-PTRA) and 8 weeks post-PTRA, stented quantifiable scanned kidneys.
Time frame: Baseline (pre-PTRA) and 8 weeks post-PTRA
Population: All participants with stented quantifiable kidneys for whom GFR by MDCT was measured at Baseline (pre-PTRA) and 8 weeks post-PTRA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bendavia | Change in Mean Glomerular Flow Rate as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Right Single Kidney | 0.238 mL/min | Standard Deviation 0.2557 |
| Bendavia | Change in Mean Glomerular Flow Rate as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Left Single Kidney | 0.012 mL/min | Standard Deviation 0.1487 |
| Placebo | Change in Mean Glomerular Flow Rate as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Right Single Kidney | 0.010 mL/min | Standard Deviation 0.0552 |
| Placebo | Change in Mean Glomerular Flow Rate as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Left Single Kidney | 0.120 mL/min | Standard Deviation 0.16 |
Secondary
Change in Mean Regional Perfusion as Measured by MDCT at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA
Change in mean regional perfusion as measured by Multi-Detector Computed Tomography (MDCT) Baseline (pre-PTRA) and 8 weeks post-PTRA for stented quantifiable scanned kidneys.
Time frame: Baseline (pre-PTRA) and 8 weeks post-PTRA
Population: All participants for whom regional perfusion was measured by MDCT with stented quantifiable scanned kidneys at Baseline (pre-PTRA) and 8 weeks post-PTRA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bendavia | Change in Mean Regional Perfusion as Measured by MDCT at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Right Cortical | 1.266 mL/min | Standard Deviation 0.9341 |
| Bendavia | Change in Mean Regional Perfusion as Measured by MDCT at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Right Medullary | 0.242 mL/min | Standard Deviation 0.4143 |
| Bendavia | Change in Mean Regional Perfusion as Measured by MDCT at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Left Cortical | 0.614 mL/min | Standard Deviation 1.239 |
| Bendavia | Change in Mean Regional Perfusion as Measured by MDCT at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Left Medullary | 0.150 mL/min | Standard Deviation 0.3788 |
| Placebo | Change in Mean Regional Perfusion as Measured by MDCT at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Left Medullary | 0.156 mL/min | Standard Deviation 0.5184 |
| Placebo | Change in Mean Regional Perfusion as Measured by MDCT at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Right Cortical | -0.816 mL/min | Standard Deviation 0.6614 |
| Placebo | Change in Mean Regional Perfusion as Measured by MDCT at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Left Cortical | 0.220 mL/min | Standard Deviation 0.9112 |
| Placebo | Change in Mean Regional Perfusion as Measured by MDCT at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Right Medullary | -0.082 mL/min | Standard Deviation 0.2541 |
Secondary
Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA
Change in mean renal blood flow (ml/minute) as measured using Multi-Detector Computed Tomography (MDCT) at Baseline (pre-PTRA) and 8 weeks post-PTRA for stented quantifiable scanned kidneys
Time frame: Baseline (pre-PTRA) and 8 weeks post-PTRA
Population: All participants for whom renal blood flow as measured by MDCT was measured in stented quantifiable scanned kidneys at baseline and 8 weeks post-PTRA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bendavia | Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Right Cortical | 85.056 mL/min | Standard Deviation 63.2943 |
| Bendavia | Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Right Total | 91.712 mL/min | Standard Deviation 82.4794 |
| Bendavia | Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Left Total | 27.538 mL/min | Standard Deviation 78.0728 |
| Bendavia | Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Left Cortical | 23.928 mL/min | Standard Deviation 64.4891 |
| Bendavia | Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Right Medullary | 6.658 mL/min | Standard Deviation 20.3007 |
| Bendavia | Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Left Medullary | 3.610 mL/min | Standard Deviation 14.4951 |
| Placebo | Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Right Medullary | -10.204 mL/min | Standard Deviation 21.2044 |
| Placebo | Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Left Total | 41.018 mL/min | Standard Deviation 75.6824 |
| Placebo | Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Right Cortical | -28.406 mL/min | Standard Deviation 54.8919 |
| Placebo | Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Left Medullary | 5.930 mL/min | Standard Deviation 19.0256 |
| Placebo | Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Right Total | -38.608 mL/min | Standard Deviation 43.4011 |
| Placebo | Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA | Left Cortical | 35.090 mL/min | Standard Deviation 59.947 |
Secondary
Change in Mean Renal Volume as Measured by Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA.
Change in mean renal volume as measured by Multi-Detector Computed Tomography (MDCT) at Baseline (pre-PTRA) and 8 weeks post-PTRA.
Time frame: Baseline (Pre-PTRA) and 8 (+4) weeks post-PTRA
Population: All participants for whom renal volume was measured at baseline (Pre-PTRA) and 8 weeks post-PTRA in stented quantifiable kidneys.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bendavia | Change in Mean Renal Volume as Measured by Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Right Cortical | 4.372 mL | Standard Deviation 10.5438 |
| Bendavia | Change in Mean Renal Volume as Measured by Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Left Cortical | 4.534 mL | Standard Deviation 15.0459 |
| Bendavia | Change in Mean Renal Volume as Measured by Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Right Medullary | -3.162 mL | Standard Deviation 4.7616 |
| Bendavia | Change in Mean Renal Volume as Measured by Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Left Total Kidney Volume | 5.090 mL | Standard Deviation 17.6951 |
| Bendavia | Change in Mean Renal Volume as Measured by Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Left Medullary | 0.558 mL | Standard Deviation 3.1016 |
| Bendavia | Change in Mean Renal Volume as Measured by Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Right Total Kidney Volume | 1.270 mL | Standard Deviation 12.8218 |
| Placebo | Change in Mean Renal Volume as Measured by Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Left Medullary | 0.120 mL | Standard Deviation 8.6277 |
| Placebo | Change in Mean Renal Volume as Measured by Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Right Total Kidney Volume | 4.708 mL | Standard Deviation 13.7198 |
| Placebo | Change in Mean Renal Volume as Measured by Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Left Total Kidney Volume | 10.220 mL | Standard Deviation 8.9447 |
| Placebo | Change in Mean Renal Volume as Measured by Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Right Cortical | 9.840 mL | Standard Deviation 13.1156 |
| Placebo | Change in Mean Renal Volume as Measured by Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Left Cortical | 10.100 mL | Standard Deviation 10.8462 |
| Placebo | Change in Mean Renal Volume as Measured by Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA. | Right Medullary | -5.132 mL | Standard Deviation 7.067 |
Secondary
Mean Change in Diastolic Blood Pressure
Mean Change in Diastolic Blood Pressure (DBP) values (mmHg) from baseline (pre-PTRA), immediately post-PTRA, 27 hours and 8 weeks post-PTRA, with and without Bendavia.
Time frame: Pre-PTRA, immediately post-PTRA, 27 hours post-PTRA and 8 weeks post-PTRA
Population: All participants for whom diastolic blood pressure was measured.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bendavia | Mean Change in Diastolic Blood Pressure | 27 Hours Post-PTRA | 3.6 mmHg | Standard Deviation 7.76 |
| Bendavia | Mean Change in Diastolic Blood Pressure | 8 Weeks Post PTRA | 0.0 mmHg | Standard Deviation 9.7 |
| Placebo | Mean Change in Diastolic Blood Pressure | 27 Hours Post-PTRA | -2.0 mmHg | Standard Deviation 9.88 |
| Placebo | Mean Change in Diastolic Blood Pressure | 8 Weeks Post PTRA | 0.1 mmHg | Standard Deviation 9.8 |
Secondary
Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA
Mean change in renal oxygenation, axial aspect, in stented kidneys between baseline (pre-PTRA), and 27 hours post-PTRA and 8 weeks post-PTRA as measured by calculation of fractional hypoxia using blood oxygenation level-dependent magnetic resonance (BOLD-MR) imaging.
Time frame: Baseline (Pre-PTRA) , 27 hours post-PTRA and 8 weeks post-PTRA
Population: All participants for whom fractional renal oxygenation, axial aspect, in stented kidneys was measured at baseline, 27 hours post-PTRA and 8 weeks post-PTRA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bendavia | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialRightPrefurosemideFractHyp%>20 27H Post PTRA | 13.440 s^-1 | Standard Deviation 34.6825 |
| Bendavia | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialRightPostfurosemideFracHyp%>20 8WkPostPTRA | 28.625 s^-1 | Standard Deviation 8.9537 |
| Bendavia | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialLeft Post-FurosemideFrac Hyp%>20 27HPostPTRA | 0.148 s^-1 | Standard Deviation 21.0184 |
| Bendavia | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialRightPrefurosemideFractHyp%>20; 8Wk Post PTRA | -3.380 s^-1 | Standard Deviation 8.5013 |
| Bendavia | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialRightPostfurosemideFracHyp%>30 8WkPost PTRA | -0.400 s^-1 | Standard Deviation 2.9473 |
| Bendavia | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialLeft PrefurosemideFrac Hyp %>30 8Wk PostPTRA | -0.602 s^-1 | Standard Deviation 7.151 |
| Bendavia | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialLeftPrefurosemide Frac Hyp%>20 27H Post PTRA | 1.320 s^-1 | Standard Deviation 21.7694 |
| Bendavia | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialRightPrefurosemideFractHyp%>30 27H PostPTRA | 5.206 s^-1 | Standard Deviation 9.4875 |
| Bendavia | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialLeftPrefurosemide Frac Hyp%>20 8Wk Post PTRA | -0.420 s^-1 | Standard Deviation 17.3066 |
| Bendavia | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialRightPostfurosemideFracHyp %30 27H Post PTRA | 6.080 s^-1 | Standard Deviation 7.6904 |
| Bendavia | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialLeft Prefurosemide Frac Hyp %>30 27H PostPTRA | -3.128 s^-1 | Standard Deviation 3.0154 |
| Bendavia | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialLeft Post-FurosemideFrac Hyp%>20 8WkPostPTRA | -0.012 s^-1 | Standard Deviation 17.3829 |
| Bendavia | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialRightPrefurosemideFractHyp%>30 8Wk PostPTRA | -2.120 s^-1 | Standard Deviation 2.7426 |
| Bendavia | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialLeft Post-FurosemideFrac Hyp%>30 27HPostPTRA | -1.874 s^-1 | Standard Deviation 2.5111 |
| Bendavia | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialRightPostfurosemideFracHyp%>20 27HPostPTRA | 24.280 s^-1 | Standard Deviation 27.6206 |
| Bendavia | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialLeft Post-FurosemideFrac Hyp%>30 8WkPostPTRA | 1.858 s^-1 | Standard Deviation 7.0087 |
| Placebo | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialRightPostfurosemideFracHyp%>20 27HPostPTRA | 13.854 s^-1 | Standard Deviation 26.2292 |
| Placebo | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialLeft Prefurosemide Frac Hyp %>30 27H PostPTRA | 16.938 s^-1 | Standard Deviation 25.4089 |
| Placebo | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialLeft PrefurosemideFrac Hyp %>30 8Wk PostPTRA | -6.360 s^-1 | Standard Deviation 11.3054 |
| Placebo | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialLeft Post-FurosemideFrac Hyp%>20 27HPostPTRA | 14.083 s^-1 | Standard Deviation 34.6825 |
| Placebo | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialLeft Post-FurosemideFrac Hyp%>30 8WkPostPTRA | -5.704 s^-1 | Standard Deviation 8.355 |
| Placebo | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialRightPrefurosemideFractHyp%>20 27H Post PTRA | 16.708 s^-1 | Standard Deviation 19.498 |
| Placebo | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialRightPrefurosemideFractHyp%>20; 8Wk Post PTRA | -10.892 s^-1 | Standard Deviation 15.37 |
| Placebo | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialRightPrefurosemideFractHyp%>30 27H PostPTRA | 11.600 s^-1 | Standard Deviation 17.8192 |
| Placebo | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialRightPrefurosemideFractHyp%>30 8Wk PostPTRA | -1.840 s^-1 | Standard Deviation 2.8693 |
| Placebo | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialRightPostfurosemideFracHyp%>20 8WkPostPTRA | -7.560 s^-1 | Standard Deviation 13.5471 |
| Placebo | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialRightPostfurosemideFracHyp %30 27H Post PTRA | 13.490 s^-1 | Standard Deviation 21.1322 |
| Placebo | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialRightPostfurosemideFracHyp%>30 8WkPost PTRA | -1.370 s^-1 | Standard Deviation 3.4412 |
| Placebo | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialLeftPrefurosemide Frac Hyp%>20 27H Post PTRA | 12.767 s^-1 | Standard Deviation 26.0745 |
| Placebo | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialLeftPrefurosemide Frac Hyp%>20 8Wk Post PTRA | -8.160 s^-1 | Standard Deviation 16.4477 |
| Placebo | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialLeft Post-FurosemideFrac Hyp%>20 8WkPostPTRA | -14.220 s^-1 | Standard Deviation 13.303 |
| Placebo | Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA | AxialLeft Post-FurosemideFrac Hyp%>30 27HPostPTRA | 18.757 s^-1 | Standard Deviation 27.1441 |
Secondary
Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA
Mean change in renal oxygenation, coronal aspect, in stented kidneys between baseline (pre-PTRA) and 27 hours post-PTRA or 8 weeks post-PTRA, as measured by calculation of fractional hypoxia using blood oxygenation level-dependent magnetic resonance (BOLD-MR) imaging, with and without Bendavia
Time frame: 27H post PTRA and 8 weeks Post PTRA
Population: All participants for whom fractional renal oxygenation, coronal aspect, in stented kidneys was measured at baseline, 27 hours post-PTRA and 8 weeks post-PTRA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bendavia | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalRtFractHypoxia% >20Prefuros.27HPost-PTRA | 20.314 s^-1 | Standard Deviation 33.3525 |
| Bendavia | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalLeftFractHypoxia% >20Prefuros.27HPost-PTRA | 5.000 s^-1 | Standard Deviation 23.7674 |
| Bendavia | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalLeftFractHypoxia% >30Prefuros.8WkPost-PTRA | -2.275 s^-1 | Standard Deviation 4.465 |
| Bendavia | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalRtFractHypoxia% >20Prefuros.8WkPost-PTRA | 4.140 s^-1 | Standard Deviation 16.469 |
| Bendavia | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalRtFractHypoxia% >30Prefuros.27HPost-PTRA | 10.800 s^-1 | Standard Deviation 9.6734 |
| Bendavia | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalRtFractHypoxia% >30Prefuros8WkPost-PTRA | 3.300 s^-1 | Standard Deviation 10.1403 |
| Bendavia | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalRtFractHypoxia% >20Postfuros27HPost-PTRA | 29.800 s^-1 | Standard Deviation 33.5328 |
| Bendavia | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalRtFractHypoxia% >20Postfuros8WKPost-PTRA | 5.233 s^-1 | Standard Deviation 7.5142 |
| Bendavia | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalRtFractHypoxia% >30Postfuros27HPost-PTRA | 12.875 s^-1 | Standard Deviation 13.2666 |
| Bendavia | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalRtFractHypoxia% >30Postfuros8WkPost-PTRA | 2.233 s^-1 | Standard Deviation 3.5119 |
| Bendavia | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalLeftFractHypoxia% >20Prefuros.8WkPost-PTRA | -3.125 s^-1 | Standard Deviation 10.297 |
| Bendavia | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalLeftFractHypoxia% >30Prefuros.27HPost-PTRA | -2.000 s^-1 | Standard Deviation 8.9272 |
| Bendavia | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalLeftFractHypoxia% >20Postfuros.27HPost-PTRA | 6.240 s^-1 | Standard Deviation 24.5671 |
| Bendavia | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalLeftFractHypoxia% >20Postfuros.8WkPost-PTRA | 3.375 s^-1 | Standard Deviation 9.2525 |
| Bendavia | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalLeftFractHypoxia% >30Postfuros.27HPost-PTRA | 0.080 s^-1 | Standard Deviation 7.3145 |
| Bendavia | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalLeftFractHypoxia% >30Postfuros.8WkPost-PTRA | -0.250 s^-1 | Standard Deviation 2.0873 |
| Placebo | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalLeftFractHypoxia% >20Postfuros.27HPost-PTRA | 6.783 s^-1 | Standard Deviation 29.1337 |
| Placebo | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalRtFractHypoxia% >30Prefuros.27HPost-PTRA | 9.250 s^-1 | Standard Deviation 30.6001 |
| Placebo | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalRtFractHypoxia% >30Postfuros8WkPost-PTRA | -8.158 s^-1 | Standard Deviation 16.5393 |
| Placebo | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalLeftFractHypoxia% >20Prefuros.27HPost-PTRA | 6.033 s^-1 | Standard Deviation 31.182 |
| Placebo | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalRtFractHypoxia% >20Prefuros.27HPost-PTRA | 9.083 s^-1 | Standard Deviation 17.3368 |
| Placebo | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalLeftFractHypoxia% >30Postfuros.27HPost-PTRA | 20.345 s^-1 | Standard Deviation 31.5024 |
| Placebo | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalRtFractHypoxia% >20Prefuros.8WkPost-PTRA | -2.220 s^-1 | Standard Deviation 7.5549 |
| Placebo | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalLeftFractHypoxia% >20Prefuros.8WkPost-PTRA | -0.525 s^-1 | Standard Deviation 12.5077 |
| Placebo | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalLeftFractHypoxia% >20Postfuros.8WkPost-PTRA | -0.700 s^-1 | Standard Deviation 14.7384 |
| Placebo | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalRtFractHypoxia% >30Prefuros8WkPost-PTRA | -2.852 s^-1 | Standard Deviation 11.1986 |
| Placebo | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalLeftFractHypoxia% >30Prefuros.27HPost-PTRA | 22.615 s^-1 | Standard Deviation 35.6971 |
| Placebo | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalRtFractHypoxia% >20Postfuros27HPost-PTRA | 3.840 s^-1 | Standard Deviation 22.4825 |
| Placebo | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalLeftFractHypoxia% >30Prefuros.8WkPost-PTRA | -1.525 s^-1 | Standard Deviation 12.3605 |
| Placebo | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalRtFractHypoxia% >20Postfuros8WKPost-PTRA | -5.220 s^-1 | Standard Deviation 4.6018 |
| Placebo | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalLeftFractHypoxia% >30Postfuros.8WkPost-PTRA | -4.225 s^-1 | Standard Deviation 12.7899 |
| Placebo | Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA | CoronalRtFractHypoxia% >30Postfuros27HPost-PTRA | 11.458 s^-1 | Standard Deviation 32.8826 |
Secondary
Mean Change in Systolic Blood Pressure Values (mmHg) From Pre-PTRA, Immediately Post-PTRA, 27 Hours and 8 (+4) Weeks Post-PTRA
Time frame: Pre-PTRA and 27 hours post-PTRA and 8 weeks post-PTRA
Population: All participants for whom systolic blood pressure was measured at baseline (pre-PTRA) and 27 hours post-PTRA, or 8(+4) weeks post-PTRA.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bendavia | Mean Change in Systolic Blood Pressure Values (mmHg) From Pre-PTRA, Immediately Post-PTRA, 27 Hours and 8 (+4) Weeks Post-PTRA | 27 Hours Post-PTRA | -2.9 mmHg | Standard Deviation 14.78 |
| Bendavia | Mean Change in Systolic Blood Pressure Values (mmHg) From Pre-PTRA, Immediately Post-PTRA, 27 Hours and 8 (+4) Weeks Post-PTRA | 8 weeks Post PTRA | 13.2 mmHg | Standard Deviation 19.88 |
| Placebo | Mean Change in Systolic Blood Pressure Values (mmHg) From Pre-PTRA, Immediately Post-PTRA, 27 Hours and 8 (+4) Weeks Post-PTRA | 27 Hours Post-PTRA | -3.8 mmHg | Standard Deviation 15.69 |
| Placebo | Mean Change in Systolic Blood Pressure Values (mmHg) From Pre-PTRA, Immediately Post-PTRA, 27 Hours and 8 (+4) Weeks Post-PTRA | 8 weeks Post PTRA | -0.8 mmHg | Standard Deviation 30.83 |