AzTrials
AzTrials

Heart FailurePhase 2NCT01096043

A Dose-Defining Study of CXL-1020 in Patients With Systolic Heart Failure

A Phase 2 study testing Strata 1 CXL-1020, Strata 2 CXL-1020 and Strata 3 CXL-1020 in people with Heart Failure, run by Bristol-Myers Squibb at 15 sites in United States.

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

Study CXL-1020-02 employs is designed to further define suitable clinical dosages for CXL-1020 which will be utilized in a later Phase IIb study. The study is conducted in 3 different stages called 'strata" and evaluates the potential utility of this drug for the treatment of patents who are hospitalized with heart… Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Heart Failure
What is being tested?
Strata 1 CXL-1020, Strata 2 CXL-1020 and Strata 3 CXL-1020
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
69 participants
Where
15 sitesUnited States
Study dates
Apr 2010to Feb 2012
Phase
Phase 2
Are there results?
None posted in the registry

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

  • In order to be eligible for randomization, a patient MUST:
  • Be a male or post menopausal or surgically sterile female requiring inpatient evaluation or treatment and be between 18 and 85 years of age
  • Not require immediate emergent treatment with conventional parenteral inotropes or vasodilators
  • Be receiving standard background heart failure therapies as indicated, but not receive an oral dose of a hemodynamically active treatment or diuretic within 3 hours of baseline hemodynamic assessments
  • Have chronic Systolic HF due to primary/idiopathic dilated cardiomyopathy, coronary artery disease or hypertension
  • For inclusion in the Non-Invasive Strata B, have a baseline (within 48 hours prior to dosing) left ventricular ejection fraction ≤ 35% estimated from a baseline 2D-Echocardiogram
Show all 15Show fewer
  • For inclusion in the Invasive Strata A and C, have baseline hemodynamic values (mean of 3 consecutive CI measurements taken within 1 hours preceding dosing within 10% of one another with a mean CI of less than or equal to (≤) 2.5L/min AND a mean PCWP of greater than 20mmHg
  • Have an elevated baseline BNP of at least 400pg/ml in all protocol strata
  • Be capable of understanding the nature of the trial and be willing to participate as documented by written informed consent
  • Be willing and able to comply with the inpatient and outpatient study protocol requirements for the duration of the study (treatment plus 30 follow up at days)
  • If a post-menopausal or surgically sterile female, confirmation of sterility status (post-menopausal or surgically sterile for at least 6 months; post-menopausal subjects will require a urine pregnancy test for confirmation)
  • If a fertile male, must be using 2 approved contraceptive methods (a condom and a spermicidal agent, even if partner(s) is using birth control) for 10 days following participation in the study and further agree to not donate sperm for 10 days after participation in the study
  • Must have a negative urine test for drugs of abuse and a negative ethanol breath test or blood test at baseline before dosing
  • Have required local laboratory safety data within protocol required or local laboratory non-exclusionary ranges before dosing
  • May be receiving ICD, Bi V pacing or rate control pacing at the time of randomization so long as no alteration of settings are anticipated within the day of study drug administration

Who cannot join

  • In order to be eligible for randomization, a patient MUST NOT:
  • Have participated in any investigational drug study, SERCa gene therapy or cellular myocardial transplant study within 30 days preceding randomization or have previously received therapy with CXL-1020
  • Have received a parenteral or oral dose of diuretics or other hemodynamically active therapy within 3 hours of the baseline hemodynamic assessment
  • Have received intravenous inotropes, inodilators or vasodilators (amrinone, digoxin, dopamine, dobutamine, enoximone, levosimendan, milrinone, nesiritide, nitroglycerine or nitroprusside) for more than 4 hours and within 12 hours prior to randomization to treatment with study drug
  • Have a heart rate <50 or ≥ 90 BPM at baseline prior to randomization
  • Have a blood pressure >150 Systolic and/or >95 diastolic mmHg at baseline prior to randomization
Show all 23Show fewer
  • Have a systolic blood pressure of less than 100 mmHg at baseline prior to randomization
  • Be in atrial fibrillation/flutter at the time of randomization or have a history of recent intermittent A-fib/flutter within the previous week
  • Have non-sustained VT (HR > 120 bpm) of 10 beats or more during bedside monitoring prior to randomization or excessive VPB's or complex multifocal ventricular ectopy exceeding 10 beats per minute on a 2 minute rhythm strip taken within 10 minutes prior to randomization
  • Have a history of successful cardiac resuscitation within the past 2 years. (Inappropriate ICD firings for non lethal arrhythmias are not exclusionary)
  • Be hospitalized with acute coronary syndrome or acute myocardial infarction during the previous 90 days prior to randomization
  • Have a history of stroke (CVA) or transient ischemic attack (TIA) within six months prior to randomization
  • Have a concurrent history of CCS Class III or IV angina
  • Be a patient whose HF etiology is attributable to either restrictive/obstructive cardiomyopathy, idiopathic hypertrophic cardiomyopathy (as defined by any wall thickness > 1.8 cm) or uncorrected severe valvular disease
  • Be receiving concomitant oral or parenteral therapy with any antiarrhythmic drugs other than amiodarone or dronedarone. (only oral therapy is allowed for these agents)
  • Have unsuitable echocardiographic windows for the Echo assessments (applies only to Strata B)
  • Have a screening or baseline serum Na < 130 mEq/l or > 145 mEq/l; a serum K < 3.5 mEq/l or > 5.5 mEq/l; a serum Ca < 7.5 mg/dl or > 10.2 mg/dl; or a serum Mg < 1.6 mEq/l or > 3.0 mEq/l., or a digoxin level above 1ng/ml
  • Have a baseline serum creatinine > 2.5 mg/dl; an ALT or AST >3 times the upper normal limit; or a hemoglobin < 10 g/dl
  • Have taken ethanol within 24 hours (with a positive ethanol breath test or blood test) or a PDE5 inhibitor within 96 hours of study drug administration
  • Have other clinically significant laboratory or medical conditions that, in the opinion of the Investigator, make the patient unsuitable for evaluation in the study
  • Be receiving a drug which is expected to possess the potential for a clinically significant pharmacokinetic interaction with CXL-1020, as defined in the investigational drug brochure (IDB).
  • Be the recipient of a myocardial restraint device or flap
  • Have an anticipated survival of less than 90 days for any reason Note: Patients receiving cardiac resynchronization therapy for HF are eligible and pacemaker settings have not been changed on this hospitalization and can be left unchanged for the study.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Cincinnati

    Cincinnati, Ohio, 45267

  • University Hospitals Case Medical Center

    Cleveland, Ohio, 44106

  • Davis Heart & Lung Research Institute

    Columbus, Ohio, 43210

  • DMC Cardiovascular Institute

    Detroit, Michigan, 48201

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • University of Florida

    Gainesville, Florida, 32610

  • Stern Cardiovascular Center PA

    Germantown, Tennessee, 38138

  • University of Florida

    Jacksonville, Florida, 32209

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • Florida Hospital Transplant Center

    Orlando, Florida, 32804

  • University of Medicine & Dentistry of New Jersey - New Jersey Medical School

    South Orange, New Jersey, 07103

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: A Phase IIa, 3 Strata Dose-Defining Study Evaluating the Hemodynamic Effects, Safety and Tolerability of CXL-1020 in Patients With Systolic Heart Failure

Study CXL-1020-02 employs is designed to further define suitable clinical dosages for CXL-1020 which will be utilized in a later Phase IIb study. The study is conducted in 3 different stages called 'strata" and evaluates the potential utility of this drug for the treatment of patents who are hospitalized with heart failure.

Read the detailed description

Each of the 3 strata are described below:

Invasive Strata 1: This is a randomized, double-blinded stratum that will enroll up to 65 patients who are hospitalized with symptomatic heart failure who have indwelling PA catheters allowing invasive hemodynamic evaluation. Each patient will receive a six hour intravenous infusion of either placebo or CXL-1020.

Non-Invasive Strata 2: This is a randomized, double-blinded stratum which will enroll up to approximately 72 patients (in several cohorts with 12-24 patients each) who neither require, nor have in place, an indwelling PA catheter for hemodynamic monitoring, but meet study entrance criteria for symptoms of heart failure, (dyspnea at rest)and systolic dysfunction by specific echocardiography criteria. Monitoring of drug effects will be performed by Echocardiography.

Invasive-Strata 3: This is a randomized, double-blinded stratum that will begin after an evaluation of a substantial number of patients in Strata A and B and will enroll approximately 15-30 patients using the same general enrollment criteria as in Invasive Strata A.

Conditions
Heart Failure
Being tested
Placebo, Strata 1 CXL-1020, Strata 2 CXL-1020, Strata 3 CXL-1020
Keywords
Heart Failure, ADHF
Medical subject headings
Heart Failure

What participants receive

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

  • PlaceboDrug

    Also called BMS-986233

    An infusion of an identically appearing solution of sugar water will be intravenously administered.

  • Strata 1 CXL-1020Drug

    Also called BMS-986233

    Intravenous infusion of CXL-1020, up-titrated, so that 3 different dosages are administered over 6 hours

  • Strata 2 CXL-1020Drug

    Also called BMS-986233

    One of 3 different dosages of CXL-1020 administered at a fixed dosage level for 6 hours.

  • Strata 3 CXL-1020Drug

    Also called BMS-986233

    A fixed dose level of CXL-1020 will be administered for the initial 6 hours of treatment in Strata 3 and then dosage will be altered up or downward based on the investigators observation of the patient's condition.

Study groups in NCT01096043
Study groupRoleWhat they receive
PlaceboPlacebo comparatorEach Strata of the study will have a placebo control. In strata A, the chance of getting active drug is 4 out of 5, in Strata B the chance of getting active drug is 3 ot of 4, and in Strata C, the chance of getting active Drug is 4 out of 5. In the event that a patient is allocated to receive placebo, the treatment may be stopped if the patient's condition fails to improve or worsens during the placebo infusion.
Receives: Drug: Placebo
Strata 1 CXL-1020ExperimentalPatients assigned to CXL-1020 in strata one will have their dose increased from the initial dose 2 times during the study period. The treatment may be stopped if the patient's condition fails to improve or worsens during the infusion.
Receives: Drug: Strata 1 CXL-1020
Strata 2 CXL-1020ExperimentalIn strata 2, patients who are assigned to active treatment will receive one of up to 3 possible fixed dose levels of CXL-1020 for a period of 6 hours. The treatment may be stopped if the patient's condition fails to improve or worsens during the infusion.
Receives: Drug: Strata 2 CXL-1020
Strata 3 CXL-1020ExperimentalIn strata 3, patients assigned to receive CXL-1020 will receive a fixed dose of CXL-1020 for 6 hours, and then the dose may be increased or decreased, based on the investigators assessment of the patient. The treatment may be stopped if the patient's condition fails to improve or worsens during the infusion.
Receives: Drug: Strata 3 CXL-1020

What is being measured

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

  1. Safety and Hemodynamic Effects

    Define the safety and hemodynamic benefit of CXL-1020 based upon the change from baseline in hemodynamic measurements at the 6 hour time point in all strata

    Measured: At 6 Hours following start of dosing

Secondary outcomes (5)

  1. Measurement of Plasma BNP Levels

    Evaluate the effects of CXL-1020 on change from baseline in circulating BNP levels after 6 hours of treatment in all strata.

    Measured: At 6 hours following the start of dosing

  2. Assessment of the dose/plasma concentration/effect relationship of CXL-1020

    Correlation of plasma concentrations of the CXL-1020 metabolites with Drug Hemodynamic Effects

    Measured: At 6 hours following start of dosing

  3. Effects of CXL-1020 on Renal Function

    Evaluate effects of CXL-1020 on renal function parameters (serum creatinine, Cystatin C, and plasma NGAL)

    Measured: 24 hours post dosing

  4. Signs and Symptoms of Heart failure

    Evaluate heart failure symptoms in using a Likert 7-point heart failure symptom scale completed by the Investigator and a visual analogue scale completed by the patient and after the 6 hour timepoint in Stratum C

    Measured: At 6 hours following the start of dosing

  5. Evaluation of all Adverse Events

    Assess adverse events within 30 days of treatment as adjudicated by an independent safety committee (all strata)

    Measured: Through 30 days following study drug dosing

Timeline

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

  1. First posted30 Mar 2010 (estimated)
  2. Study startApr 2010
  3. Primary completionFeb 2012
  4. Study completionFeb 2012

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
69 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01096043
Sponsor's protocol ID
CXL-1020-02
Status last verified
Apr 2012
First submitted
22 Mar 2010
Last updated
15 Nov 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • Sabbah HN, Tocchetti CG, Wang M, Daya S, Gupta RC, Tunin RS, Mazhari R, Takimoto E, Paolocci N, Cowart D, Colucci WS, Kass DA. Nitroxyl (HNO): A novel approach for the acute treatment of heart failure. Circ Heart Fail. 2013 Nov;6(6):1250-8. doi: 10.1161/CIRCHEARTFAILURE.113.000632. Epub 2013 Oct 9.

    PubMed 24107588

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Strata 1 CXL-1020, Strata 2 CXL-1020 and Strata 3 CXL-1020 in people with Heart Failure, run by Bristol-Myers Squibb at 15 sites 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 23 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 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites 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 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Safety and Hemodynamic Effects (time frame: At 6 Hours following start of dosing). 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 NCT01096043, 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 Nov 2016.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in