Renal Artery ObstructionPhase 1/2EVOLVENCT01755858
Effects of Intravenous Bendavia™ on Reperfusion Injury in Patients Undergoing Angioplasty of the Renal Artery
A Phase 1/2 study testing Bendavia in people with Renal Artery Obstruction and Hypertension, Renovascular, run by Stealth BioTherapeutics Inc. at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Renal Artery Obstruction, Hypertension, Renovascular, Ischemia Reperfusion Injury
- What is being tested?
- Bendavia
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2012to May 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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.
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- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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).
Read the 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.
- Being tested
- Bendavia, Placebo
- Keywords
- elamipretide
- Medical subject headings
- Renal Artery Obstruction, Hypertension, Renovascular, Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BendaviaDrug
Also called MTP-131, Elamipretide
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Bendavia | Experimental | Bendavia, intravenous infusion, 0.05 mg/kg/hr for a maximum duration of 4 hours. Receives: Drug: Bendavia |
| Placebo | Placebo comparator | Placebo (no active drug), intravenous infusion, for a maximum duration of 4 hours. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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..
Measured: Baseline (pre-PTRA) and 8 weeks post-PTRA
Secondary outcomes (8)
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.
Measured: 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
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.
Measured: 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
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
Measured: 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.
Change in mean renal volume as measured by Multi-Detector Computed Tomography (MDCT) at Baseline (pre-PTRA) and 8 weeks post-PTRA.
Measured: Baseline (Pre-PTRA) and 8 (+4) 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
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.
Measured: 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, 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
Measured: 27H 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
Measured: Pre-PTRA and 27 hours post-PTRA and 8 weeks post-PTRA
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.
Measured: Pre-PTRA, immediately post-PTRA, 27 hours post-PTRA and 8 weeks post-PTRA
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2012 (estimated)
- Study startDec 2012
- Primary completionDec 2015
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renal Artery ObstructionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stealth BioTherapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stephen C Textor, MD, Principal investigator, Mayo ClinicRichard Straube, MD, Study director, Stealth BioTherapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01755858
- Sponsor's protocol ID
- SPIRI-225
- Acronym
- EVOLVE
- Status last verified
- Aug 2020
- First submitted
- 19 Dec 2012
- Last updated
- 11 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 28916603
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01755858
- Acronym / sponsor ID
- EVOLVE / SPIRI-225
- Keywords
- elamipretide
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Stealth BioTherapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2012
- Primary completion
- Dec 2015 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 24 Dec 2012 (estimated)
- Results
- Posted 11 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bendavia | Experimental | Drug: BendaviaBendavia, intravenous infusion, 0.05 mg/kg/hr for a maximum duration of 4 hours. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo (no active drug), intravenous infusion, for a maximum duration of 4 hours. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- ≥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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BendaviaAlso: MTP-131, Elamipretide | Drug | Bendavia |
| Placebo | Drug | Placebo |
Primary outcome
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..
8 secondary outcomes
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 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 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 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
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, 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 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
Mean Change in Diastolic Blood Pressure
Time frame: Pre-PTRA, immediately post-PTRA, 27 hours post-PTRA and 8 weeks post-PTRA
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28916603Saad 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen C Textor, MD principal investigator
Mayo Clinic
Richard Straube, MD study director
Stealth BioTherapeutics Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bendavia in people with Renal Artery Obstruction and Hypertension, Renovascular, run by Stealth BioTherapeutics Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: Baseline (pre-PTRA) and 8 weeks post-PTRA). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01755858, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2020.