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

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ClinicalTrials.gov Identifier: NCT01755858
Recruitment Status : Terminated
First Posted : December 24, 2012
Results First Posted : August 11, 2020
Last Update Posted : August 11, 2020
Sponsor:
Information provided by (Responsible Party):
Stealth BioTherapeutics Inc.

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).

Condition or disease Intervention/treatment Phase
Renal Artery Obstruction Hypertension, Renovascular Ischemia Reperfusion Injury Drug: Bendavia Drug: Placebo Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase 2a, Placebo-controlled Trial to Evaluate the Impact of Intravenous Bendavia™ on Ischemia Reperfusion Injury in Atherosclerotic Renal Artery Stenosis in Patients Undergoing Percutaneous Transluminal Angioplasty of the Renal Artery
Study Start Date : December 2012
Actual Primary Completion Date : December 2015
Actual Study Completion Date : May 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Angioplasty

Arm Intervention/treatment
Experimental: Bendavia
Bendavia, intravenous infusion, 0.05 mg/kg/hr for a maximum duration of 4 hours.
Drug: Bendavia
Other Names:
  • MTP-131
  • Elamipretide

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



Primary Outcome Measures :
  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 ]
    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 Outcome Measures :
  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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01755858


Locations
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United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Stealth BioTherapeutics Inc.
Investigators
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Principal Investigator: Stephen C Textor, MD Mayo Clinic
Study Director: Richard Straube, MD Stealth BioTherapeutics Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Stealth BioTherapeutics Inc.
ClinicalTrials.gov Identifier: NCT01755858    
Other Study ID Numbers: SPIRI-225
First Posted: December 24, 2012    Key Record Dates
Results First Posted: August 11, 2020
Last Update Posted: August 11, 2020
Last Verified: August 2020
Keywords provided by Stealth BioTherapeutics Inc.:
elamipretide
Additional relevant MeSH terms:
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Renal Artery Obstruction
Hypertension, Renovascular
Reperfusion Injury
Ischemia
Wounds and Injuries
Hypertension
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Postoperative Complications
Kidney Diseases
Urologic Diseases
Arterial Occlusive Diseases
Hypertension, Renal