Clinical trial NCT01755858: Effects of Intravenous Bendavia™ on Reperfusion Injury in Patients Undergoing Angioplasty of the Renal Artery
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Renal Artery Obstruction
Hypertension, Renovascular
Ischemia Reperfusion Injury
Keywords: elamipretide
Lead sponsor: Stealth BioTherapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2012-12-24
Enrollment: 16
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility 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.

Primary outcomes:
measure: Change in Mean Glomerular Filtration Rate (GFR), as Measured by Iothalamate Clearance, at Baseline (Pre-percutaneous Renal Artery Angioplasty and 8 Weeks Post-PTRA.
timeFrame: Baseline (pre-PTRA) and 8 weeks post-PTRA
Secondary outcomes:
measure: Change in Mean Glomerular Flow Rate as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA.
timeFrame: Baseline (pre-PTRA) and 8 weeks post-PTRA
measure: Change in Mean Regional Perfusion as Measured by MDCT at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA
timeFrame: Baseline (pre-PTRA) and 8 weeks post-PTRA
measure: Change in Mean Renal Blood Flow as Measured Using Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA
timeFrame: Baseline (pre-PTRA) and 8 weeks post-PTRA
measure: Change in Mean Renal Volume as Measured by Multi-Detector Computed Tomography (MDCT) at Baseline (Pre-PTRA) and 8 Weeks Post-PTRA.
timeFrame: Baseline (Pre-PTRA) and 8 (+4) weeks post-PTRA
measure: Mean Change in Renal Oxygenation, Axial Aspect, in Stented Kidneys From Baseline (Pre-PTRA), and 27 Hours Post-PTRA and 8 Weeks Post-PTRA
timeFrame: Baseline (Pre-PTRA) , 27 hours post-PTRA and 8 weeks post-PTRA
measure: Mean Change in Renal Oxygenation, Coronal Aspect, in Stented Kidneys Between Baseline Pre-PTRA, 27 Hours Post-PTRA and 8 Weeks Post-PTRA
timeFrame: 27H post PTRA and 8 weeks Post PTRA
measure: Mean Change in Systolic Blood Pressure Values (mmHg) From Pre-PTRA, Immediately Post-PTRA, 27 Hours and 8 (+4) Weeks Post-PTRA
timeFrame: Pre-PTRA and 27 hours post-PTRA and 8 weeks post-PTRA
measure: Mean Change in Diastolic Blood Pressure
timeFrame: Pre-PTRA, immediately post-PTRA, 27 hours post-PTRA and 8 weeks post-PTRA
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Stephen C Textor, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stealth BioTherapeutics Inc.
name: Richard Straube, MD
role: STUDY_DIRECTOR
References:
citation: Saad A, Herrmann SMS, Eirin A, Ferguson CM, Glockner JF, Bjarnason H, McKusick MA, Misra S, Lerman LO, Textor SC. Phase 2a Clinical Trial of Mitochondrial Protection (Elamipretide) During Stent Revascularization in Patients With Atherosclerotic Renal Artery Stenosis. Circ Cardiovasc Interv. 2017 Sep;10(9):e005487. doi: 10.1161/CIRCINTERVENTIONS.117.005487.