AKIPhase 2STARTNCT04564833
Effect of RBT-1 on Preconditioning Response Biomarkers in Subjects Undergoing CABG and/or Cardiac Valve Surgery
A Phase 2 study testing Low Dose RBT-1 and High Dose RBT-1 in people with AKI, run by Renibus Therapeutics, Inc. at 25 sites in 3 countries.
Trial summary
The purpose of this study is to evaluate the effect of RBT-1 (stannous protoporphyrin [SnPP]/iron sucrose [FeS]) on preconditioning response biomarkers in subjects who are at risk for AKI following cardiac surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AKI
- What is being tested?
- Low Dose RBT-1 and High Dose RBT-1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 152 participants
- Where
- 25 sitesin 3 countries
- Study dates
- 4 Aug 2021to 3 Feb 2023
- Phase
- Phase 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects ≥18 years of age at Screening.
- Able and willing to comply with all study procedures.
- Stable kidney function per Investigator assessment and no known episodes of AKI during the preceding 4 weeks.
- Scheduled to undergo non-emergent coronary and/or valve surgery(ies) requiring cardiopulmonary bypass, including:
- CABG alone;
- Combined CABG surgery/repair of 1 or more cardiac valves;
Show all 9Show fewer
- Cardiac valve(s) replacement or repair alone.
- Females and males of childbearing potential must agree to use 2 forms of contraception, with at least 1 being a barrier method, or abstain from sexual activity for 30 days following study drug administration.
- Male subjects must agree not to donate or sell sperm for 30 days following study drug administration.
Who cannot join
- Presence of AKI (KDIGO criteria) at the time of Screening.
- Surgery to be performed without cardiopulmonary bypass.
- Surgery to be performed under conditions of circulatory arrest or hypothermia with rectal temperature <28°C (82.4°F).
- eGFR ≤20 mL/min/1.73m2 or need for dialysis.
- Surgery for aortic dissection or to correct a major congenital heart defect.
- Administration of iodinated contrast media within 24 hours prior to cardiac surgery or evidence of contrast-induced nephropathy prior to cardiac surgery.
Show all 26Show fewer
- Cardiogenic shock or hemodynamic instability within the 24 hours prior to surgery and requirement for inotropes or vasopressors or other mechanical devices, such as intra-aortic balloon counter-pulsation.
- Requirement for any of the following within 7 days prior to cardiac surgery:
- Defibrillator or permanent pacemaker;
- Mechanical ventilation;
- Intra-aortic balloon counter-pulsation;
- Left ventricular assist device;
- Other forms of mechanical circulatory support.
- Known history of cancer within the past 2 years, except for carcinoma in situ of the cervix or adequately treated basal cell carcinoma of the skin.
- Known or suspected sepsis at time of Screening or confirmed or treated endocarditis within 30 days prior to cardiac surgery.
- Other current active infection requiring systemic antibiotic treatment.
- Inadequate hepatic function, defined as total bilirubin or alanine aminotransferase or aspartate aminotransferase >2X the upper limit of normal at time of Screening or Child Pugh Class C liver disease or higher.
- Any congenital coagulation disorder.
- Asplenia (anatomic or functional).
- History of photosensitivity or active skin disease that, in the opinion of the Investigator, could be worsened by RBT-1.
- Known hypersensitivity or previous anaphylaxis to SnPP or any tin-based product.
- Serum ferritin >500 ng/mL or those who have received IV iron within 28 days of Screening.
- Pregnancy or lactation.
- Treatment with an investigational drug or participation in an interventional study within 30 days prior to administration of study drug.
- In the opinion of the Investigator, any disease processes or confounding variables that would inappropriately alter the outcome of the study.
- Inability to comply with the requirements of the study protocol.
Trial locations and contacts
25 sites in 3 countries.
25 sites in 3 countries
United States18 sites
Indiana University Health Southern Indiana
Bloomington, Indiana, 47403
Brigham and Women's Hospital
Boston, Massachusetts, 02115
University of Chicago Hospital Anesthesia and Critical Care
Chicago, Illinois, 60637
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
New York Presbyterian-Queens
Flushing, New York, 11355
Lutheran Medical Group
Fort Wayne, Indiana, 46804
Heart Center Research, LLC
Huntsville, Alabama, 35801
McLaren Greater Lansing
Lansing, Michigan, 48910
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Keck Hospital of USC
Los Angeles, California, 90033
MyMichigan Medical Center
Midland, Michigan, 48670
Yale University School of Medicine
New Haven, Connecticut, 06519
Columbia University Irving Medical Center
New York, New York, 10032
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Rochester General Hospital Center for Clinical Research
Rochester, New York, 14621
Santa Barbara Cottage Hospital
Santa Barbara, California, 93102
Stanford University Medical Center
Stanford, California, 94305
MedStar Health Research Institute, Inc.
Washington D.C., District of Columbia, 20010
Australia4 sites
Flinders Medical Centre
Bedford Park, South Australia
Monash Medical Centre
Clayton, Victoria
The Alfred Hospital
Melbourne, Victoria, 3004
Gold Cost University Hospital & Health Services
Southport, Queensland, 4215
Canada3 sites
Hamilton Health Sciences Corporation
Hamilton, Ontario, L8L 2X2
Institut Universitaire de Cardiologie et de Pneumologie de Québec
Québec, Quebec, G1V 4G5
St-John Regional Hospital
Saint John, New Brunswick, E2L 4L2
About this study
Official title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effect of RBT-1 on Preconditioning Response Biomarkers in Subjects Undergoing Coronary Artery Bypass Graft (CABG) and/or Cardiac Valve Surgery (The START Study)
The purpose of this study is to evaluate the effect of RBT-1 (stannous protoporphyrin [SnPP]/iron sucrose [FeS]) on preconditioning response biomarkers in subjects who are at risk for AKI following cardiac surgery.
- Conditions
- AKI
- Being tested
- Low Dose RBT-1, High Dose RBT-1, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Dose RBT-1Drug
intravenous administration
High Dose RBT-1Drug
intravenous administration
PlaceboDrug
intravenous administration
| Study group | Role | What they receive |
|---|---|---|
| Low Dose RBT-1 | Experimental | Single IV infusion prior to cardiac surgery Receives: Drug: Low Dose RBT-1 |
| High Dose RBT-1 | Experimental | Single IV infusion prior to cardiac surgery Receives: Drug: High Dose RBT-1 |
| Placebo | Placebo comparator | Single IV infusion prior to cardiac surgery Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the Efficacy of RBT-1 in Generating a Preconditioning Response as Measured by a Composite of Biomarkers
Composite of the geometric mean of the ratios of the maximum PreOp value over Baseline for plasma heme oxygenase-1 (HO-1), ferritin, and interleukin-10 (IL-10)
Measured: Baseline through Pre-Surgery
Secondary outcomes (3)
Change in Renal Tubular Injury Biomarkers
Geometric mean of the ratios of the maximum PostOp value over Baseline for urine KIM-1, NGAL, and cystatin C.
Measured: Baseline through Day 3 post-cardiac surgery
Number of Subjects With Reduction in Urine Output
Documented AE of sustained reduction in urine output, oliguria, or anuria post-cardiac surgery through Day 5
Measured: Baseline through post-cardiac surgery through Day 5
Number of Subjects With Acute Kidney Injury (AKI)
AKI is defined using the KDIGO criteria (ie, an absolute increase in serum creatinine of ≥1.5 × Baseline; or documented AE of sustained reduction in urine output, oliguria, or anuria; or initiation of dialysis).
Measured: Baseline through Day 5 post-cardiac surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2020
- Study start4 Aug 2021
- Primary completion9 Nov 2022
- Study completion3 Feb 2023
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 AKIStudies 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will be randomized 1:1:1 to low dose RBT-1, high dose RBT-1, and placebo
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 152 participants (actual)
Sponsor and investigators
- Lead sponsor
- Renibus Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04564833
- Sponsor's protocol ID
- REN-004
- Acronym
- START
- Status last verified
- Apr 2024
- First submitted
- 21 Sep 2020
- Last updated
- 15 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lamy A, Chertow GM, Jessen M, Collar A, Brown CD, Mack CA, Marzouk M, Scavo V, Washburn TB, Savage D, Smith J, Bennetts J, Assi R, Shults C, Arghami A, Butler J, Devereaux PJ, Zager R, Wang C, Snapinn S, Browne A, Rodriguez J, Ruiz S, Singh B; of START Investigators. Effects of RBT-1 on preconditioning response biomarkers in patients undergoing coronary artery bypass graft or heart valve surgery: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. EClinicalMedicine. 2024 Jan 8;68:102364. doi: 10.1016/j.eclinm.2023.102364. eCollection 2024 Feb.
PubMed 38586479
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effect of RBT-1 on Preconditioning Response Biomarkers in Subjects Undergoing Coronary Artery Bypass Graft (CABG) and/or Cardiac Valve Surgery (The START Study)
- ClinicalTrials.gov ID
- NCT04564833
- Acronym / sponsor ID
- START / REN-004
- Conditions
- AKI
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 152 participants (actual)
- Lead sponsor
- Renibus Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 4 Aug 2021 (actual)
- Primary completion
- 9 Nov 2022 (actual)
- Study completion
- 3 Feb 2023 (actual)
- First posted
- 25 Sep 2020 (actual)
- Results
- Posted 16 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the effect of RBT-1 (stannous protoporphyrin [SnPP]/iron sucrose [FeS]) on preconditioning response biomarkers in subjects who are at risk for AKI following cardiac surgery.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- Model description
- Subjects will be randomized 1:1:1 to low dose RBT-1, high dose RBT-1, and placebo
| Arm | Type | Receives |
|---|---|---|
| Low Dose RBT-1 | Experimental | Drug: Low Dose RBT-1Single IV infusion prior to cardiac surgery |
| High Dose RBT-1 | Experimental | Drug: High Dose RBT-1Single IV infusion prior to cardiac surgery |
| Placebo | Placebo comparator | Drug: PlaceboSingle IV infusion prior to cardiac surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female subjects ≥18 years of age at Screening.
- Able and willing to comply with all study procedures.
- Stable kidney function per Investigator assessment and no known episodes of AKI during the preceding 4 weeks.
- Scheduled to undergo non-emergent coronary and/or valve surgery(ies) requiring cardiopulmonary bypass, including:
- Females and males of childbearing potential must agree to use 2 forms of contraception, with at least 1 being a barrier method, or abstain from sexual activity for 30 days following study drug administration.
Key exclusion criteria (26 listed)
- Presence of AKI (KDIGO criteria) at the time of Screening.
- Surgery to be performed without cardiopulmonary bypass.
- Surgery to be performed under conditions of circulatory arrest or hypothermia with rectal temperature <28°C (82.4°F).
- eGFR ≤20 mL/min/1.73m2 or need for dialysis.
- Surgery for aortic dissection or to correct a major congenital heart defect.
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 |
|---|---|---|
| Low Dose RBT-1intravenous administration | Drug | Low Dose RBT-1 |
| High Dose RBT-1intravenous administration | Drug | High Dose RBT-1 |
| Placebointravenous administration | Drug | Placebo |
Primary outcome
Evaluate the Efficacy of RBT-1 in Generating a Preconditioning Response as Measured by a Composite of Biomarkers
Time frame: Baseline through Pre-Surgery
Composite of the geometric mean of the ratios of the maximum PreOp value over Baseline for plasma heme oxygenase-1 (HO-1), ferritin, and interleukin-10 (IL-10)
3 secondary outcomes
Change in Renal Tubular Injury Biomarkers
Time frame: Baseline through Day 3 post-cardiac surgery
Number of Subjects With Reduction in Urine Output
Time frame: Baseline through post-cardiac surgery through Day 5
Number of Subjects With Acute Kidney Injury (AKI)
Time frame: Baseline through Day 5 post-cardiac surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 38586479Lamy A, Chertow GM, Jessen M, Collar A, Brown CD, Mack CA, Marzouk M, Scavo V, Washburn TB, Savage D, Smith J, Bennetts J, Assi R, Shults C, Arghami A, Butler J, Devereaux PJ, Zager R, Wang C, Snapinn S, Browne A, Rodriguez J, Ruiz S, Singh B; of START Investigators. Effects of RBT-1 on preconditioning response biomarkers in patients undergoing coronary artery bypass graft or heart valve surgery: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. EClinicalMedicine. 2024 Jan 8;68:102364. doi: 10.1016/j.eclinm.2023.102364. eCollection 2024 Feb.
- Effects of RBT-1 on preconditioning response biomarkers in patients undergoing coronary artery bypass graft or heart valve surgery: a multicentre, double-blind, randomised, placebo-controlled phase 2 trialLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for AKI
Not yet recruiting
Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial
Acute-on-Chronic Liver Failure (ACLF)
Recruiting
Acute Kidney Injury and Ultra-endurance Running
AKI (Acute Kidney Injury) Due to Trauma
Not yet recruiting
Neuromuscular Electrical Stimulation to Improve the Muscle Health of Individuals With Acute Kidney Injury
Acute Kidney Injury, Acute Kidney Injury KDIGO 2
Recruiting
Clinical Decision Support for SGLT2i After AKI in Type 2 Diabetes
Type 2 Diabetes Mellitus, Acute Kidney Injury
Not yet recruiting
Precision-Medicine Diagnostic Support in Hospitalized Veterans With Acute Kidney Injury
Acute Kidney Injury (AKI)
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.
The record lists no contact. Use the official record to reach the sponsor.
25 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low Dose RBT-1 and High Dose RBT-1 in people with AKI, run by Renibus Therapeutics, Inc. at 25 sites in 3 countries.
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 9 inclusion and 26 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: finished, as of the sponsor's last update on 15 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, Australia, Canada. 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 phase mean?
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 16 Jan 2024). 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?
Evaluate the Efficacy of RBT-1 in Generating a Preconditioning Response as Measured by a Composite of Biomarkers (time frame: Baseline through Pre-Surgery). 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 NCT04564833, 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 15 Apr 2024.