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Trial · Interventional

TerminatedPhase 1/2Results postedRegistry data

Effects of Intravenous Bendavia™ on Reperfusion Injury in Patients Undergoing Angioplasty of the Renal Artery

Short name EVOLVE

Overview

Status
Terminated
Phase
Phase 1/2
Enrollment
16 participants (actual)
Sponsor
Stealth BioTherapeutics Inc. · Industry
Design
Randomized · Triple masking
Countries
1 country

United States

Start
Dec 2012
Primary completion
Dec 2015
Completion
May 2016
First posted
24 Dec 2012 (estimated)
Last update posted
11 Aug 2020
Conditions
Renal Artery Obstruction · Hypertension, Renovascular · Ischemia Reperfusion Injury

Timeline

1 trial · 1 stopped early · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201220132014201520162017
  1. Ph 1/2

    EVOLVE

    NCT01755858

    Dec 2012 to May 2016

    Terminated

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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).

Interventions

  • BendaviaDrug
  • PlaceboDrug

Arms2

  • Experimental

    Bendavia

    Bendavia, intravenous infusion, 0.05 mg/kg/hr for a maximum duration of 4 hours.

  • Placebo comparator

    Placebo

    Placebo (no active drug), intravenous infusion, for a maximum duration of 4 hours.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Change in Mean Glomerular Filtration Rate (GFR), as Measured by Iothalamate Clearance, at Baseline (Pre-percutaneous Renal Artery Angioplasty and 8 Weeks Post-PTRA.

    Time frame · Baseline (pre-PTRA) and 8 weeks post-PTRA

    Registry description

    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 outcomes(8)
  1. Change in Mean Glomerular Flow Rate as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA.

    Time frame · Baseline (pre-PTRA) and 8 weeks post-PTRA

    Registry description

    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.

  2. Change in Mean Regional Perfusion as Measured by MDCT at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA

    Time frame · Baseline (pre-PTRA) and 8 weeks post-PTRA

    Registry description

    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.

  3. Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA

    Time frame · Baseline (pre-PTRA) and 8 weeks post-PTRA

    Registry description

    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

  4. 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

    Registry description

    Change in mean renal volume as measured by Multi-Detector Computed Tomography (MDCT) at Baseline (pre-PTRA) and 8 weeks post-PTRA.

  5. Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA

    Time frame · Baseline (Pre-PTRA) , 27 hours post-PTRA and 8 weeks post-PTRA

    Registry description

    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.

  6. Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA

    Time frame · 27H post PTRA and 8 weeks Post PTRA

    Registry description

    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

  7. 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

  8. Mean Change in Diastolic Blood Pressure

    Time frame · Pre-PTRA, immediately post-PTRA, 27 hours post-PTRA and 8 weeks post-PTRA

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Baseline (pre-PTRA) and 8 weeks post-PTRA

Change in Mean Glomerular Filtration Rate (GFR), as Measured by Iothalamate Clearance, at Baseline (Pre-percutaneous Renal Artery Angioplasty and 8 Weeks Post-PTRA.

GroupValue (mL/min)Spread
Bendavia6.312.14
Placebo12.023.84
Secondary and other outcome results(7)
Secondary outcomeMean· 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.

GroupValue (mL/min)Spread
Bendavia0.2380.2557
Placebo0.0100.0552
Secondary outcomeMean· Baseline (pre-PTRA) and 8 weeks post-PTRA

Change in Mean Regional Perfusion as Measured by MDCT at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA

GroupValue (mL/min)Spread
Bendavia1.2660.9341
Placebo-0.8160.6614
Secondary outcomeMean· Baseline (pre-PTRA) and 8 weeks post-PTRA

Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA

GroupValue (mL/min)Spread
Bendavia85.05663.2943
Placebo-28.40654.8919
Secondary outcomeMean· 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.

GroupValue (mL)Spread
Bendavia1.27012.8218
Placebo4.70813.7198
Secondary outcomeMean· Baseline (Pre-PTRA) , 27 hours post-PTRA and 8 weeks post-PTRA

Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA

GroupValue (s^-1)Spread
Bendavia13.44034.6825
Placebo16.70819.4980
Secondary outcomeMean· 27H post PTRA and 8 weeks Post PTRA

Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA

GroupValue (s^-1)Spread
Bendavia20.31433.3525
Placebo9.08317.3368
Secondary outcomeMean· Pre-PTRA and 27 hours post-PTRA and 8 weeks post-PTRA

Mean Change in Systolic Blood Pressure Values (mmHg) From Pre-PTRA, Immediately Post-PTRA, 27 Hours and 8 (+4) Weeks Post-PTRA

GroupValue (mmHg)Spread
Bendavia-2.914.78
Placebo-3.815.69

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
BendaviaBendavia, intravenous infusion, 0.05 mg/kg/hr for a maximum duration of 4 hours.0 / 71 / 72 / 7
PlaceboPlacebo (no active drug), intravenous infusion, for a maximum duration of 4 hours.0 / 91 / 95 / 9

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2017

5 results

Phase 2a Clinical Trial of Mitochondrial Protection (Elamipretide) During Stent Revascularization in Patients With Atherosclerotic Renal Artery Stenosis.

Saad et al. 2017Circulation. Cardiovascular interventionscited by 95

PMID 28916603PMC5659347DOI 10.1161/circinterventions.117.005487PUB-28916603

Rights unknown5 results

Eligibility

Who could join, as posted.

Sex
All
Age
from 40 Years up to 80 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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.

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