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Acute Kidney InjuryPhase 2NCT01830920

A Study of THR-184 in Patients at Risk of Developing Cardiac Surgery Associated-Acute Kidney Injury (CSA-AKI)

A Phase 2 study testing THR-184 in people with Acute Kidney Injury, run by Thrasos Innovation, Inc. at 41 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to determine whether THR-184 when administered around the time of cardiac surgery that requires cardiopulmonary bypass can prevent or ameliorate the development of acute kidney injury. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Acute Kidney Injury
What is being tested?
THR-184
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
452 participants
Where
41 sitesin 2 countries
Study dates
May 2013to Sep 2015
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 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female and >18 years of age.
  • Scheduled for a non-emergent coronary and/or valve surgery procedure requiring CPB, to include:
  • coronary artery bypass graft (CABG) alone;
  • aortic valve replacement or repair alone, with or without aortic root repair;
  • mitral, tricuspid, or pulmonic valve replacement or repair alone;
  • simultaneous replacement of several cardiac valves;
Show all 21Show fewer
  • CABG with aortic, mitral, tricuspid, or pulmonic valve replacement or repair;
  • CABG with combined cardiac valve replacement or repair.
  • Have the following risk factors for CSA-AKI:
  • eGFR ≥ 20 and < 30 ml/min/1.73m2 OR
  • eGFR ≥ 30 and < 60 ml/min/1.73m2 and ONE of the following additional risk factors (other than age ≥ 75 years) OR
  • eGFR ≥ 60 ml/min/1.73m2 and TWO of the following additional risk factors
  • Additional Risk Factors:
  • Age ≥ 75 years;
  • Combined valve \& coronary surgery;
  • Previous cardiac surgery with sternotomy;
  • Documented NYHA Class III or IV within 1 year prior to surgery;
  • Left ventricular ejection fraction (LVEF) ≤ 35% by invasive or noninvasive diagnostic cardiac imaging - echocardiography, nuclear imaging, computed tomography, magnetic resonance imaging or angiography performed within 90 days prior to surgery. (If LVEF ≤ 35% by any invasive or noninvasive imaging procedure, patient meets the risk factor.)
  • Insulin-requiring diabetes;
  • Non-insulin-requiring diabetes and the presence of ≥+2 proteinuria on urinalysis (medical history or dipstick);
  • Preoperative anemia (hemoglobin <11g/dl for men and women).

Who cannot join

  • If any of the following criteria apply prior to surgery, the patient will be excluded from the study:
  • Age > 85 years;
  • Weight >174 kg or 383 lbs;
  • The presence of AKI (KDIGO criteria) at the time of screening ;
  • Surgery to be performed without CPB;
  • Surgery to be performed under conditions of circulatory arrest or hypothermia with rectal temperature < 28°Celsius (82.4° Fahrenheit);
Show all 40Show fewer
  • eGFR (MDRD) <20 ml/min/1.73m2;
  • Surgery for aortic dissection;
  • Surgery to correct a major congenital heart defect (e.g., Tetralogy of Fallot, transposition of the great vessels, single ventricle, Ebsteins anomaly. Bicuspid aortic valve is not to be considered a congenital heart defect.);
  • Prior organ transplantation;
  • Dialysis-dependence;
  • Administration of iodinated contrast media within 24 hours prior to cardiac surgery;
  • If received contrast media prior to 24 hours and have AKI as defined by KDIGO criteria;
  • Cardiogenic shock or haemodynamic instability within the 24 hours prior to surgery, including the anesthesia induction period; as defined by a systolic BP <80 mm Hg and pulse >120 beats per minute (bpm) and requirement for inotropes or vasopressors or other mechanical devices such as intra-aortic balloon counter-pulsation (IABP);
  • Requirement for any of the following within seven (7) days prior to cardiac surgery:
  • defibrillator or permanent pacemaker,
  • mechanical ventilation,
  • intra-aortic balloon counter-pulsation (IABP),
  • left ventricular assist device (LVAD),
  • other forms of mechanical circulatory support (MCS);
  • Cardiopulmonary resuscitation within 14 days prior to cardiac surgery;
  • Known history of cancer within the past 5 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;
  • Known or suspected glomerulonephritis or interstitial nephritis at time of screening;
  • Confirmed or treated endocarditis within previous 30 days prior to cardiac surgery;
  • Other current active infection requiring antibiotic treatment;
  • Patients with known active human immunodeficiency virus infection;
  • Documented history of HIV antibodies;
  • Patients with known active Hepatitis B (HBV) or Hepatitis C (HCV) infection;
  • Documented history of HCV antibodies;
  • Documented history of HBV antigens;
  • Patients on immunosuppressant drugs or prednisone over the dose of 20 mg per day;
  • Inadequate hepatic function, defined as total bilirubin or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times the upper limit of normal (ULN) at time of screening or Child Pugh Class C liver disease ( see appendix 6) or higher;
  • Any congenital coagulation disorder;
  • Pregnancy or lactation;
  • If patient has "Do Not Resuscitate" (DNR) status;
  • Known hypersensitivity to the study drug or any of its excipients;
  • Treatment with an investigational drug or participation in an interventional trial within 60 days prior to 1st dose 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

41 sites in 2 countries.

41 sites in 2 countries

United States31 sites

  • St. Peter's Hospital

    Albany, New York, 12208

  • John Hopkins University

    Baltimore, Maryland, 21287

  • Suburban Hospital

    Bethesda, Maryland, 20814

  • University of Alabama-Birmingham

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Erlanger Health System

    Chattanooga, Tennessee, 37404

  • Memorial Hospital

    Chattanooga, Tennessee, 37404

  • University of Chicago

    Chicago, Illinois, 60637

  • Lindner Research Center-Christ Hospital

    Cincinnati, Ohio, 45219

  • The Ohio State University Medical Center

    Columbus, Ohio, 43210

  • Baylor University Medical Center, Soltero Cardiovascular Research Center

    Dallas, Texas, 75226

  • Danbury Hospital

    Danbury, Connecticut, 06810

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Durham VA Medical Center

    Durham, North Carolina, 27710

  • Indiana Ohio Heart

    Fort Wayne, Indiana, 46804

  • University of Texas, Houston

    Houston, Texas, 77030

  • Indiana Heart-St. Vincent Medical Group

    Indianapolis, Indiana, 46290

  • River City Clinical Research

    Jacksonville, Florida, 32207

  • University of Southern California

    Los Angeles, California, 90033

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37212

  • Columbia University

    New York, New York, 10032

  • Advocate Christ Medical Center

    Oak Lawn, Illinois, 60453

  • St. Joseph's Regional Medical Center

    Paterson, New Jersey, 07503

  • Cardiac and Vascular Research Center of Northern Michigan

    Petoskey, Michigan, 49770

  • Maine Medical Center

    Portland, Maine, 04102

  • Cardiothoracic Surgical Associates

    Richmond, Virginia, 23225

  • Covenant Medical Center

    Saginaw, Michigan, 48602

  • Baystate Medical Center

    Springfield, Massachusetts, 01199

  • Washington University

    St Louis, Missouri, 63110

  • Stanford University

    Stanford, California, 94305

  • Harbor - University of California Los Angeles Medical Center

    Torrance, California, 90503

Other trials in United States

Canada10 sites

  • Foothills Medical Centre

    Calgary, Alberta, T2N 2T9

  • Hamilton Health Sciences Corporation

    Hamilton, Ontario, L8L 2X2

  • Institut de Cardiologie de Montréal

    Montreal, Quebec, H1T 1C8

  • Centre hospitalier de l'université de Montréal(CHUM)- Hôtel-Dieu

    Montreal, Quebec, H2W 1T8

  • MUHC - Royal Victoria Hospital

    Montreal, Quebec, H3A 1A1

  • Sacre Cœur Hospital

    Montreal, Quebec, H4J 1C5

  • University of Ottawa Heart Institute

    Ottawa, Ontario, K1Y 4W7

  • Institut Universitaire de Cardiologie et de Pneumologie de Québec

    Québec, Quebec, G1V 4G5

  • St-John Regional Hospital Facility

    Saint John, New Brunswick, E2L4L2

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

Other trials in Canada

About this study

Official title: A Multi-Center, Parallel-Group, Randomized, Double Blind, Adaptive Study Investigating the Safety and Efficacy of THR-184 in Patients at Increased Risk of Developing Cardiac Surgery Associated-Acute Kidney Injury (CSA-AKI)

The purpose of this study is to determine whether THR-184 when administered around the time of cardiac surgery that requires cardiopulmonary bypass can prevent or ameliorate the development of acute kidney injury.

Read the detailed description

The study has been designed to include patients scheduled for cardiac surgery who are considered at increased risk for developing CSA-AKI. The eligibility criteria are intended to enrich the study population with such patients.

Stage 1 consisted of 140 patients randomized in a 1:1:1:1 ratio (approximately 35 patients per treatment arm) to Placebo or to one of three (3) THR-184 dose arms:

  • initial pre-surgery low dose of THR-184 by three (3) post-surgery doses at the low dose, or
  • initial pre-surgery middle dose of THR-184 followed by three (3) post-surgery doses at the low dose, or
  • initial pre-surgery high dose of THR-184 followed by three (3) post-surgery doses at the low dose

An interim analysis (IA) was performed by the Independent Statistical Center (ISC) and presented to the Independent Data Monitoring Committee (IDMC). The IDMC indicated no safety concerns and recommended that the study continue with the placebo arm and the initial pre-surgery high dose arm. Additionally, another dosing arm will be added, which will increase the dose post-surgery.

Stage 2 will consist of approximately 270 patients randomized in a 1:1:2 ratio to Placebo or to a dose selected from one of the two (2) THR-184 dose arms:

  • initial pre-surgery high dose of THR-184, followed by (3) post-surgery doses at the original low dose;
  • initial pre-surgery high dose of THR-184, followed by (3) post-surgery doses at ~80% of the pre-surgery dose

Study treatment (THR-184 or placebo) will consist of one 60-minute IV infusion administered prior to surgery, followed by a 60-minute IV infusion administered, beginning in the early post-operative period, and followed by two (2) additional 60-minute IV infusions administered, on consecutive days post-cardiac surgery.

The primary endpoint for the evaluation of efficacy in patients receiving THR-184, as compared to patients receiving Placebo, will be the proportion of patients developing CSA-AKI as measured by the Kidney Disease Improving Global Outcomes (KDIGO) criteria, as follows:

  • Increase in Serum creatinine (SCr) by ≥0.3 mg/dl (>26.5 µmol/l) within 48 hours post-surgery; or
  • Increase in SCr to ≥1.5 times a baseline which has been measured in the previous 7 days; or
  • Urine volume <0.5 ml/kg/h for 6 hours post-operatively

If at least one of these measures is present by the 7 day assessment, a patient will be considered to have developed CSA-AKI.

Being tested
THR-184, Placebo
Keywords
Acute Kidney Injury, AKI, Cardiac surgery
Medical subject headings
Acute Kidney Injury

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • THR-184Drug

    Also called Synthetic oligopeptide

    THR-184 is a synthetic oligopeptide administered intravenously.

  • PlaceboDrug

    Also called Saline solution

    A normal saline solution identical in appearance to the active drug solution

Study groups in NCT01830920
Study groupRoleWhat they receive
PlaceboPlacebo comparatorAn identical appearing placebo will be administered.
Receives: Drug: Placebo
THR-184 Dose 1ExperimentalTHR-184 initial pre-surgery low dose followed by (3) post surgery doses at the low dose.
Receives: Drug: THR-184
THR-184 Dose 2ExperimentalTHR-184 initial pre-surgery mid-dose followed by (3) post surgery doses at the low dose.
Receives: Drug: THR-184
THR-184 Dose 3ExperimentalTHR-184 initial pre-surgery high dose followed by (3) post surgery doses at the low dose.
Receives: Drug: THR-184
THR-184 Dose 4ExperimentalTHR-184 initial pre-surgery high dose followed by (3) post surgery doses ~80% of the pre-surgery dose.
Receives: Drug: THR-184

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Acute Kidney Injury (AKI)

    Acute kidney injury (AKI) is defined using the KDIGO criteria, in which AKI is defined as any of the following:

    • Increase in SCr by ≥0.3 mg/dl (≥26.5 µmol/l) within 48 hours; or
    • Increase in SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or
    • Urine volume <0.5 ml/kg/h for 6 hours.

    Measured: 7 days

Secondary outcomes (3)

  1. Incidence of AKI

    AKI is defined using the SCr-KDIGO criteria, defined as the following:

    • Increase in SCr by ≥0.3 mg/dl (≥26.5 µmol/l) within 48 hours; or
    • Increase in SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days.

    Measured: 7 days

  2. Severity of AKI

    AKI is defined using the KDIGO criteria, in which AKI is defined as any of the following:

    • Increase in SCr by ≥0.3 mg/dl (≥26.5 µmol/l) within 48 hours; or
    • Increase in SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or
    • Urine volume <0.5 ml/kg/h for 6 hours.

    Staging of AKI is defined as the following:

    Stage 1: SCr 1.5 - 1.9 times baseline OR ≥0.3 mg/dL (≥26.5 µmol/L) increase, Urine output <0.5 ml/kg/hr for 6-12 hours Stage 2: SCr 2.0-2.9 times baseline, Urine output <0.5 ml/kg/h for ≥ 12 hours Stage 3: SCr 3.0 times baseline OR Increase in SCr to ≥5.0 mg/dL (≥353.6 µmol/L) OR Initiation of renal replacement therapy OR In patients <18 years, decrease in eGFR to <35 ml/min per 1.73 m^2, Urine output <0.3 ml/kg/h for ≥24 hours OR Anuria for ≥12 hours.

    No AKI is considered the best outcome, and Stage 3 the worst outcome.

    Measured: 7 days

  3. Duration of AKI

    AKI is defined using the Scr-KDIGO criteria. Duration of AKI is defined as the number of days from start of AKI (SCr-KDIGO) where either SCr increase ≥ 0.3 mg/dL above pre-AKI reference point (if the value exists) or if SCr increase ≥1.5 times baseline or dialysis in the first 7 days up to discharge if prior to 7 days.

    Measured: 7 days OR up to discharge after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Apr 2013 (estimated)
  2. Study startMay 2013
  3. Primary completionSep 2015
  4. Study completionSep 2015

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
452 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01830920
Sponsor's protocol ID
A-003
Other IDs
2741202
Status last verified
Mar 2017
First submitted
10 Apr 2013
Last updated
20 Apr 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing THR-184 in people with Acute Kidney Injury, run by Thrasos Innovation, Inc. at 41 sites in 2 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 21 inclusion and 40 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 20 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in United States, 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 20 Apr 2017). 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?

Incidence of Acute Kidney Injury (AKI) (time frame: 7 days). 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 NCT01830920.

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 20 Apr 2017.

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