Heart FailurePhase 2NCT02157506

A Dose Ranging Phase IIa Study of 6 Hour Intravenous Dosages of CXL-1427 in Patients Hospitalized With Heart Failure

A Phase 2 study testing CXL-1427 in people with Heart Failure and Decompensated Heart Failure, run by Bristol-Myers Squibb at 35 sites in 5 countries.

Completed

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

Official record

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Trial summary

A randomized, double-blinded, placebo-controlled study of continuous 6-hour IV infusions of CXL-1427 in hospitalized patients with systolic heart failure. Read more about this study

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Heart Failure, Decompensated Heart Failure, Acute Heart Failure
What is being tested?: CXL-1427
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 70 participants
Where: 35 sitesin 5 countries
Study dates: 30 Jun 2014to 31 Jul 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

Inclusion Criteria -In order to be eligible for study participation, a patient MUST:
Be ≥ 18 and ≤ 85 years of age;
Have a left ventricular ejection fraction (LVEF) ≤40%, as assessed by echocardiography, a multigated acquisition (MUGA) scan or magnetic resonance imaging (MRI) within 3 months prior to or during the current hospitalization;
Be hospitalized with a primary heart failure or heart failure-related reason, e.g., acute decompensation of heart failure, transplant evaluation, hemodynamic optimization prior to ambulatory inotropes or left ventricular assist device placement;
Have an indwelling pulmonary artery (PA) catheter in place for assessment of central hemodynamic parameters; [Note: The indwelling catheter may already be in place for medically-indicated reasons, OR be placed for the primary purpose of monitoring the hemodynamic effects of the study drug. If the pulmonary artery catheter is to be placed for the sole purpose of monitoring the hemodynamic effect of the study drug, the patient must have a cardiac index (CI) ≤ 2.2L/min•m2 as measured by a non-invasive cardiac output monitor (NICaS device) ≤6 hours prior to placement of the catheter. In this setting, Exclusion Criteria 3 below also applies.]
Have a Fick and/or thermodilution determination of cardiac index ≤2.5L/min•m2 at screening, i.e., ≤4 hours before the intended start of the study drug infusion; [Note: For determinations of CI using the thermodilution method, a mean of three consecutive values measured approximately 5 minutes apart, none of which differs from the mean value by more than 15%, should be used.]

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Have a screening and baseline PCWP (or PAD, if a PCWP waveform cannot be reliably obtained) of ≥20 mmHg if systolic blood pressure is ≥100mmHg OR ≥22mmHg if systolic blood pressure is between 95-99mmHg (inclusive);
Be considered sufficiently stable to be expected not to require administration of any IV or oral vasoactive medications, including diuretics, for at least ~10 hours, i.e., from 4 hours before performing baseline hemodynamic assessments until after the completion of the 6-hour study drug infusion;
Have a body weight of at least 50kg (110 pounds), but not more than 125kg (275 pounds), and have a body mass index (BMI) <40kg/m2;
Have adequate peripheral forearm vein access or an available central line port for administration of study drug;
Be capable of understanding the nature of the trial; be willing and able to comply with the inpatient and outpatient study protocol requirements for the duration of the study (screening period, treatment period, and 30-day post-infusion follow-up period); and be willing to participate in the study, as documented by written informed consent.
Exclusion Criteria- - In order to be eligible for study participation, a patient MUST NOT:
Have a heart rate <50 or >110 beats per minute (bpm) at baseline;
Have a screening OR baseline systolic blood pressure (SBP) of >150mmHg or <100mmHg, if PCWP ≥ 20mmHg, but <22mmHg OR <95mmHg, if PCWP ≥ 22mmHg;
Have tricuspid or pulmonary valve prosthesis or endocarditis, right heart mass, a history of pneumothorax or hemothorax, a bleeding diathesis that would preclude placement of a PAL, or a history of complications from previous pulmonary artery catheter placement, when a pulmonary artery catheter is to be placed solely for the purposes of monitoring the hemodynamic effects of the study drug; In this setting, patients with multiple intracardiac leads and/or left bundle branch block should have such elective pulmonary artery catheter placement performed under radiologic guidance by experienced personnel, e.g. in the cardiac catheterization laboratory. [Note: Other pertinent history, such as trauma, vascular injury or previous surgery should guide selection of the vessel for PAL placement.]
Have a primary HF etiology attributable to either restrictive/obstructive cardiomyopathy, idiopathic hypertrophic cardiomyopathy (as defined by any wall thickness > 1.8cm) or uncorrected severe valvular disease as defined by AHA/ACC/ESC criteria;
Have been treated with dopamine, dobutamine, enoximone, nesiritide, nitroglycerine or nitroprusside within 4 hours, or with levosimendan, amrinone or milrinone within 8 hours, prior to performing baseline hemodynamic assessments, or have an anticipated need to be treated with any of these agents before the completion of the 6-hour study drug infusion;
Be receiving concomitant parenteral therapy with any antiarrhythmic drugs (oral therapy is allowed);
Be in atrial fibrillation/flutter with an uncontrolled rate (≥100bpm) at the time of randomization; [Note: Patients with a history of A-fib/flutter are eligible, if heart rate is controlled with a ventricular rate not exceeding 100bpm.]
Have non-sustained ventricular tachycardia (NSVT) of 10 beats or more during any bedside monitoring within 2 hours prior to randomization, or have excessive premature ventricular contractions (PVCs) or complex multifocal ventricular ectopy exceeding 10 beats per minute on a 2-minute rhythm strip taken within 2 hours prior to randomization;
Require, or be expected to require, any alteration of settings to an implantable cardioverter-defibrillator (ICD), single chamber or biventricular pacemaker, if applicable, from 2 hours before the intended start of the study drug infusion, until after the completion of the study drug infusion;
Have a history of sudden cardiac death/resuscitation or other appropriate ICD firing within the past 1 year. (Inappropriate ICD firings 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 a cerebral vascular accident (CVA or stroke) or of a transient ischemic attack (TIA) within 6 months prior to randomization;
Have a digoxin level above 1ng/ml (1.281nmol/L) within 8 hours before initiation of the study drug infusion;
Have persistent abnormal serum electrolytes at baseline, as defined by: a Na+ concentration <130 or >145 mEq/L, or a K+ or Mg2+ concentration outside the normal range (according to the local laboratory); [Note: Any observed electrolyte abnormalities during screening or earlier should be corrected by electrolyte supplementation and within normal acceptable concentrations should be confirmed prior to dosing. Any serum electrolyte abnormalities with associated clinical instability within 8 hours before initiation of the study drug infusion is exclusionary.]
Have an ALT or AST >3 times the upper normal limit or a hemoglobin <10g/dl (100g/L) within 8 hours before initiation of the study drug infusion;
Have a serum creatinine >2.5mg/dl (221µmol/L) or severe renal insufficiency [based on any standard limit and equation employed by the local lab, such as a GFR < 30mL/min/1.73m2 according to the Modification of Diet in Renal Disease (MDRD) equation] within 8 hours before initiation of the study drug infusion;
Have taken an oral phosphodiesterase type 5 inhibitor (PDE5) inhibitor within 96 hours before initiation of the study drug infusion;
If female, be pregnant or of child-bearing potential (i.e., female patients must be post-menopausal or surgically sterilized);
Be receiving a drug which is expected to possess a potential for a clinically significant pharmacokinetic interaction with CXL-1427, as defined in the CXL-1427 Investigator's Brochure;
Be the recipient of a myocardial restraint device or flap;
Have an anticipated survival of less than 90 days, for any reason;
Have received an investigational drug, device or biologic product within 30 days (or if longer, 5 half-lives for a drug or biologic agent) prior to randomization, or be planning to receive an investigational agent at any time throughout the full duration of the study until at least 30 days after discontinuation of study drug;
Have any other clinically significant laboratory abnormality, medical condition or social circumstance that, in the investigator's opinion, makes it inappropriate for the patient to participate in this clinical trial.

Who cannot join

None listed.

Trial locations and contacts

35 sites in 5 countries.

Country

City, postcode or hospital

35 sites in 5 countries

United States14 sites

Cardioxyl Study Site
Baltimore, Maryland, 21201
Cardioxyl Study Site
Chapel Hill, North Carolina, 27517
Cardioxyl Study Site
Charleston, South Carolina, 29425
Cardioxyl Study Site
Cincinnati, Ohio, 45267
Cardioxyl Study Site
Columbus, Ohio, 43201
Cardioxyl Study Site
Detroit, Michigan, 48202
Cardioxyl Study Site
Gainesville, Florida, 32610
Cardioxyl Study Site
Jacksonville, Florida, 32209
Cardioxyl Study Site
Jacksonville, Florida, 32224
Cardioxyl Study Site
Macon, Georgia, 31201
Cardioxyl Study Site
Nashville, Tennessee, 37232
Cardioxyl Study Site
Newark, New Jersey, 07103
Cardioxyl Study Site
Richmond, Virginia, 23298
Cardioxyl Study Site
Salt Lake City, Utah, 84132

Other trials in United States

Russia8 sites

Cardioxyl Study Site
Kemerovo, 650002
Cardioxyl Study Site
Moscow, 111539
Cardioxyl Study Site
Moscow, 121309
Cardioxyl Study Site
Moscow, 12134
Cardioxyl Study Site
Moscow, 127644
Cardioxyl Study Site
Saint Petersburg, 19242
Cardioxyl Study Site
Saint Petersburg, 199106
Cardioxyl Study Site
Tomsk, 634012

Other trials in Russia

Germany7 sites

Cardioxyl Study Site
Bad Neuheim, 61231
Cardioxyl Study Site
Cologne, 50937
Cardioxyl Study Site
Frankfurt, 60590
Cardioxyl Study Site
Göttingen, 37075
Cardioxyl Study Site
Greifswald, 17475
Cardioxyl Study Site
Kiel, 2105
Cardioxyl Study Site
Regensberg, 93053

Other trials in Germany

Poland4 sites

Cardioxyl Study Site
Lodz, 93487
Cardioxyl Study SIte
Warsaw, 01211
Cardioxyl Study Site
Warsaw, 04-628
Cardioxyl Study Site
Wroclaw, 50981

Other trials in Poland

Jordan2 sites

Cardioxyl Study Site
Amman, 11193
Cardioxyl Study Site
Irbid, 22110

Other trials in Jordan

About this study

Official title: A Phase IIa Study of the Safety, Tolerability and Hemodynamic Effects of a Continuous 6 Hour Intravenous Infusion of CXL-1427 in Hospitalized Patients With Systolic Heart Failure

A randomized, double-blinded, placebo-controlled study of continuous 6-hour IV infusions of CXL-1427 in hospitalized patients with systolic heart failure.

Read the detailed description

This is a dose finding, randomized, double-blinded, placebo-controlled study of continuous 6-hour IV infusions of CXL-1427 in hospitalized patients with systolic heart failure which will first evaluate up to four ascending dose levels of CXL-1427 in up to four cohorts of 8 patients each (the "Dose Escalation" cohorts). Subsequently, up to three of the initial dose levels of CXL-1427 may be assessed in the additional "Expansion" cohorts of up to approximately 16 patients to gain further confidence in the results at these dose levels. The CXL-1427 dose that will be evaluated in the first cohort will be 3µg/kg/min. The dose levels for the next three sequential Dose Escalation cohorts will be dependent on clinical safety and tolerability, as well as the results of the invasive hemodynamic measurements.

Conditions: Heart Failure, Decompensated Heart Failure, Acute Heart Failure
Being tested: CXL-1427, Placebo
Keywords: Acute Heart failure, Hemodynamics, Pharmacokinetics, Renal Function
Medical subject headings: Heart Failure

What participants receive

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

CXL-1427Drug
Also called BMS-986231
PlaceboDrug
Also called 5% Dextrose & 10mM potassium acetate as same IV solution diluents used in active

Study groups in NCT02157506
Study group	Role	What they receive
CXL-1427 Starting Dose	Experimental	The Starting dose of CXL-1427 in the dose escalation arms will be 3mcg/kg/min Receives: Drug: CXL-1427
CXL-1427 Dose Level 2	Experimental	The Second Dose level of CXL-1427 will be evaluated in the Dose Escalation Arm of the study as determined by the independent dose escalation committee Receives: Drug: CXL-1427
CXL-1427 Dose Level 3	Experimental	The Third Dose level of CXL-1427 will be evaluated in the Dose Escalation Arm of the study as determined by the independent dose escalation committee Receives: Drug: CXL-1427
CXL-1427 Dos Level 3	Experimental	The Third Dose level of CXL-1427 will be evaluated in the Dose Escalation Arm of the study as determined by the independent dose escalation committee Receives: Drug: CXL-1427
CXL-1427 Dose Level 4	Experimental	The forth level of CXL-1427 will be evaluated in the Dose Escalation Arm of the study as determined by the independent dose escalation committee Receives: Drug: CXL-1427
Expansion Cohort 1	Experimental	Up to 16 Patients will be enrolled across 1 or more of the previously evaluated Dose escalation Levels as determined by the independent dose escalation committee Receives: Drug: CXL-1427
Placebo for Dose Escalation and Expansion Cohort	Placebo comparator	Each Dose escalation Arm of the study will have a placebo group in a 2:1 ratio to active treatment for the first 3 patients enrolled and 4:1 to active treatment in the remaining 5 patients so that the overall randomization ratio in each Dose escalation arm will be 3:1 active to placebo. In the expansion Cohort of the study, the ratio of patients randomized to receive a 6-hour infusion of active CXL-1427 or placebo will be 3:1 Receives: Drug: Placebo

What is being measured

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

Number of Participants With Treatment-Emergent Adverse Events
A treatment-emergent adverse event (TEAE) was defined as an AE with onset after the start of the study drug infusion at Hour 00:00 through 30 days after the stop of the study drug infusion. All TEAEs and pertinent subsets of TEAEs (e.g., TEAEs with onset during the infusion of study drug, serious TEAEs, etc.) were summarized by system organ class (SOC), preferred term (PT) and treatment group
Measured: 30 days following the initiation of treatment
Mean Time Averaged Change From Baseline in Adjudicated Pulmonary Capillary Wedge Pressure (PCWP) During Infusion
The effect of CXL-1427 on PCWP is presented as the mean time-averaged change from baseline over the course of infusion of CXL-1427 or placebo in adjudicated pulmonary capillary wedge pressure (PCWP) on a modified intent-to-treat population
Measured: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion
Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Diastolic Pressure (PAD) During the Infusion
Pulmonary artery diastolic pressure (PAD) was measured by an indwelling PA catheter. Pulmonary artery diastolic pressure (PAD) approximates pulmonary capillary wedge pressure in normal individuals. The effects of CXL-1427 on time-averaged PAD during the course of the infusion are presented.
Measured: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation
Mean Time-Averaged Percent Change From Baseline in Cardiac Index (Fick)
Cardiac index is a measure of cardiac function, relating the cardiac output from the left ventricle in one minute to body surface area. It is calculated using the Fick principle, using oxygen consumption measured with a metabolic cart, hemoglobin levels, and the difference between arterial and superior vena cava oxygen saturation measured by co-oximetry. Cardiac index as calculated by the Fick method was performed using an assumed oxygen consumption value of 125 ml/min per m2 of body surface area. i.e., an assumed Fick method.
Measured: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation

Secondary outcomes (6)

Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Systolic Pressure (PAS) During the Infusion
Pulmonary artery systolic pressure (PAS) was measured by an indwelling PA catheter. The effects of CXL-1427 on time-averaged PAS during the course of the infusion are presented
Measured: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation
Mean Time-Averaged Change From Baseline in Adjudicated Right Atrial Pressure (RAP) During the Infusion
The effects of CXL-1427 on time-averaged RAP during the course of the infusion are presented
Measured: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation
Mean Time-Averaged Change From Baseline in Mean Arterial Blood Pressure (MAP) During the Infusion
Mean arterial pressure during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented
Measured: Baseline, Hour 24 after infusion, Follow-up visit 1
Mean Time-Averaged Change From Baseline in Systolic Blood Pressure (SBP) During the Infusion
Mean Time-Averaged Change from Baseline in Systolic Blood Pressure during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented
Measured: Baseline, Hour 24 after infusion, Follow-up visit 1
Mean Time-Averaged Change From Baseline in Diastolic Blood Pressure (DBP) During the Infusion
Mean Time-Averaged Change from Baseline in Diastolic Blood Pressure during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented
Measured: Baseline, Hour 24 after infusion, Follow-up visit 1
Mean Time-Averaged Change From Baseline in Heart Rate (HR) During the Infusion
Mean Time-Averaged Change from Baseline in Heart Rate during infusion of CXL-1427 or placebo on a modified intent-to-treat population is presented
Measured: Baseline, Hour 24 after infusion, Follow-up visit 1

Timeline

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

30 Jun 201431 Jul 2015

First posted6 Jun 2014 (estimated)
Study start30 Jun 2014
Primary completion31 May 2015
Study completion31 Jul 2015

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.
Other trials for Heart FailureStudies of the same condition, open and under way.
More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
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: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 70 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02157506
Sponsor's protocol ID: CXL-1427-02
Other IDs: CV013-006
Status last verified: Jul 2019
First submitted: 28 May 2014
Last updated: 31 Jul 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Heart Failure, Diastolic, Diastolic Heart Failure
Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic

All Heart Failure trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase IIa Study of the Safety, Tolerability and Hemodynamic Effects of a Continuous 6 Hour Intravenous Infusion of CXL-1427 in Hospitalized Patients With Systolic Heart Failure
ClinicalTrials.gov ID: NCT02157506
Acronym / sponsor ID: CXL-1427-02
Conditions: Heart Failure, Decompensated Heart Failure, Acute Heart Failure
Keywords: Acute Heart failure, Hemodynamics, Pharmacokinetics, Renal Function
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 70 participants (actual)
Lead sponsor: Bristol-Myers SquibbIndustry (pharma, biotech, devices)
Collaborators: Cardioxyl Pharmaceuticals, Inc
Study start: 30 Jun 2014 (actual)
Primary completion: 31 May 2015 (actual)
Study completion: 31 Jul 2015 (actual)
First posted: 6 Jun 2014 (estimated)
Results: Posted 20 May 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

A randomized, double-blinded, placebo-controlled study of continuous 6-hour IV infusions of CXL-1427 in hospitalized patients with systolic heart failure.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 7

Arm	Type	Receives
CXL-1427 Starting Dose	Experimental	Drug: CXL-1427The Starting dose of CXL-1427 in the dose escalation arms will be 3mcg/kg/min
CXL-1427 Dose Level 2	Experimental	Drug: CXL-1427The Second Dose level of CXL-1427 will be evaluated in the Dose Escalation Arm of the study as determined by the independent dose escalation committee
CXL-1427 Dose Level 3	Experimental	Drug: CXL-1427The Third Dose level of CXL-1427 will be evaluated in the Dose Escalation Arm of the study as determined by the independent dose escalation committee
CXL-1427 Dos Level 3	Experimental	Drug: CXL-1427The Third Dose level of CXL-1427 will be evaluated in the Dose Escalation Arm of the study as determined by the independent dose escalation committee
CXL-1427 Dose Level 4	Experimental	Drug: CXL-1427The forth level of CXL-1427 will be evaluated in the Dose Escalation Arm of the study as determined by the independent dose escalation committee
Expansion Cohort 1	Experimental	Drug: CXL-1427Up to 16 Patients will be enrolled across 1 or more of the previously evaluated Dose escalation Levels as determined by the independent dose escalation committee
Placebo for Dose Escalation and Expansion Cohort	Placebo comparator	Drug: PlaceboEach Dose escalation Arm of the study will have a placebo group in a 2:1 ratio to active treatment for the first 3 patients enrolled and 4:1 to active treatment in the remaining 5 patients so that the overall randomization ratio in each Dose escalation arm will be 3:1 active to placebo. In the expansion Cohort of the study, the ratio of patients randomized to receive a 6-hour infusion of active CXL-1427 or placebo will be 3:1

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (35 listed)

Inclusion Criteria -In order to be eligible for study participation, a patient MUST:
Be ≥ 18 and ≤ 85 years of age;
Have a left ventricular ejection fraction (LVEF) ≤40%, as assessed by echocardiography, a multigated acquisition (MUGA) scan or magnetic resonance imaging (MRI) within 3 months prior to or during the current hospitalization;
Be hospitalized with a primary heart failure or heart failure-related reason, e.g., acute decompensation of heart failure, transplant evaluation, hemodynamic optimization prior to ambulatory inotropes or left ventricular assist device placement;
Have an indwelling pulmonary artery (PA) catheter in place for assessment of central hemodynamic parameters; [Note: The indwelling catheter may already be in place for medically-indicated reasons, OR be placed for the primary purpose of monitoring the hemodynamic effects of the study drug. If the pulmonary artery catheter is to be placed for the sole purpose of monitoring the hemodynamic effect of the study drug, the patient must have a cardiac index (CI) ≤ 2.2L/min•m2 as measured by a non-invasive cardiac output monitor (NICaS device) ≤6 hours prior to placement of the catheter. In this setting, Exclusion Criteria 3 below also applies.]

Key exclusion criteria (0 listed)

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
CXL-1427Also: BMS-986231	Drug	CXL-1427 Dos Level 3, CXL-1427 Dose Level 2, CXL-1427 Dose Level 3, CXL-1427 Dose Level 4, CXL-1427 Starting Dose, Expansion Cohort 1
PlaceboAlso: 5% Dextrose & 10mM potassium acetate as same IV solution diluents used in active	Drug	Placebo for Dose Escalation and Expansion Cohort

Primary outcome

Number of Participants With Treatment-Emergent Adverse Events
Time frame: 30 days following the initiation of treatment
A treatment-emergent adverse event (TEAE) was defined as an AE with onset after the start of the study drug infusion at Hour 00:00 through 30 days after the stop of the study drug infusion. All TEAEs and pertinent subsets of TEAEs (e.g., TEAEs with onset during the infusion of study drug, serious TEAEs, etc.) were summarized by system organ class (SOC), preferred term (PT) and treatment group
Mean Time Averaged Change From Baseline in Adjudicated Pulmonary Capillary Wedge Pressure (PCWP) During Infusion
Time frame: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion
The effect of CXL-1427 on PCWP is presented as the mean time-averaged change from baseline over the course of infusion of CXL-1427 or placebo in adjudicated pulmonary capillary wedge pressure (PCWP) on a modified intent-to-treat population
Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Diastolic Pressure (PAD) During the Infusion
Time frame: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation
Pulmonary artery diastolic pressure (PAD) was measured by an indwelling PA catheter. Pulmonary artery diastolic pressure (PAD) approximates pulmonary capillary wedge pressure in normal individuals. The effects of CXL-1427 on time-averaged PAD during the course of the infusion are presented.
Mean Time-Averaged Percent Change From Baseline in Cardiac Index (Fick)
Time frame: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation
Cardiac index is a measure of cardiac function, relating the cardiac output from the left ventricle in one minute to body surface area. It is calculated using the Fick principle, using oxygen consumption measured with a metabolic cart, hemoglobin levels, and the difference between arterial and superior vena cava oxygen saturation measured by co-oximetry. Cardiac index as calculated by the Fick method was performed using an assumed oxygen consumption value of 125 ml/min per m2 of body surface area. i.e., an assumed Fick method.

6 secondary outcomes

Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Systolic Pressure (PAS) During the Infusion
Time frame: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation
Mean Time-Averaged Change From Baseline in Adjudicated Right Atrial Pressure (RAP) During the Infusion
Time frame: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation
Mean Time-Averaged Change From Baseline in Mean Arterial Blood Pressure (MAP) During the Infusion
Time frame: Baseline, Hour 24 after infusion, Follow-up visit 1
Mean Time-Averaged Change From Baseline in Systolic Blood Pressure (SBP) During the Infusion
Time frame: Baseline, Hour 24 after infusion, Follow-up visit 1
Mean Time-Averaged Change From Baseline in Diastolic Blood Pressure (DBP) During the Infusion
Time frame: Baseline, Hour 24 after infusion, Follow-up visit 1
Mean Time-Averaged Change From Baseline in Heart Rate (HR) During the Infusion
Time frame: Baseline, Hour 24 after infusion, Follow-up visit 1

Results and safety

Results posted to the registry on 20 May 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	12	12
CXL-1427 3μg/kg/Min	6	5
CXL-1427 5μg/kg/Min	9	8
CXL-1427 7μg/kg/Min	12	12
CXL-1427 12μg/kg/Min	7	7

Primary outcome: Number of Participants With Treatment-Emergent Adverse Events

Time frame: 30 days following the initiation of treatment. Count of participants. Unit: Participants

Measure	Placebo n = 12	CXL-1427 3μg/kg/Min n = 6	CXL-1427 5μg/kg/Min n = 9	CXL-1427 7μg/kg/Min n = 12	CXL-1427 12μg/kg/Min n = 7
At least one TEAE	3	5	5	7	3
At least one Severe TEAE	0	4	0	2	1
At least one Drug-related severe TEAE	0	0	0	0	0
At least one Serious TEAE	1	3	1	3	1
At least one Drug-related serious TEAE	0	0	0	0	0
At least one Fatal TEAE	0	1	0	0	0
At least one Drug-related fatal TEAE	0	0	0	0	0
At least one TEAE leading to drug interruption	0	0	0	0	0

Population analysed: The safety analysis set consists of all randomized participants who received all or part of the infusion of the study drug.

Primary outcome: Mean Time Averaged Change From Baseline in Adjudicated Pulmonary Capillary Wedge Pressure (PCWP) During Infusion

Time frame: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion. Mean (Standard Deviation). Unit: mm Hg

Measure	Placebo n = 12	CXL-1427 3μg/kg/Min n = 6	CXL-1427 5μg/kg/Min n = 9	CXL-1427 7μg/kg/Min n = 12	CXL-1427 12μg/kg/Min n = 7
Value	-0.17 (2.35)	-3.00 (3.06)	-5.06 (3.93)	-4.42 (4.00)	-4.75 (3.50)

Placebo vs CXL-1427 3μg/kg/Min: p =0.0059, Mixed Models Analysis
Placebo vs CXL-1427 5μg/kg/Min: p = 0.0001, Mixed Models Analysis
Placebo vs CXL-1427 7μg/kg/Min: p = 0.0062, Mixed Models Analysis

Population analysed: Modified Intent-To-Treat Analysis Set: all randomized participants who received all or part of the infusion of the study drug and had at least one baseline and post-baseline invasive hemodynamic assessment.

Primary outcome: Mean Time-Averaged Change From Baseline in Adjudicated Pulmonary Artery Diastolic Pressure (PAD) During the Infusion

Time frame: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation. Mean (Standard Deviation). Unit: mm Hg

Measure	Placebo n = 12	CXL-1427 3μg/kg/Min n = 6	CXL-1427 5μg/kg/Min n = 9	CXL-1427 7μg/kg/Min n = 12	CXL-1427 12μg/kg/Min n = 7
Value	-0.21 (3.35)	-3.69 (2.55)	-4.17 (4.02)	-2.67 (3.63)	-3.17 (1.82)

Placebo vs CXL-1427 3μg/kg/Min: p = 0.0076, Mixed Models Analysis
Placebo vs CXL-1427 5μg/kg/Min: p = 0.0052, Mixed Models Analysis
Placebo vs CXL-1427 7μg/kg/Min: p = 0.1064, Mixed Models Analysis

Population analysed: Modified Intent-To-Treat Analysis Set: all randomized patients who received all or part of the infusion of the study drug and had at least one baseline and post-baseline invasive hemodynamic assessment.

Primary outcome: Mean Time-Averaged Percent Change From Baseline in Cardiac Index (Fick)

Time frame: Baseline, Hour 2, Hour 4, Hour 6, Hour 8 post infusion initiation. Mean (Standard Deviation). Unit: Percentage of change

Measure	Placebo n = 12	CXL-1427 3μg/kg/Min n = 6	CXL-1427 5μg/kg/Min n = 9	CXL-1427 7μg/kg/Min n = 12	CXL-1427 12μg/kg/Min n = 7
Value	7.95 (16.15)	0.53 (18.12)	13.41 (23.53)	9.59 (11.91)	-9.58 (18.02)

Placebo vs CXL-1427 3μg/kg/Min: p = 0.4241, Mixed Models Analysis
Placebo vs CXL-1427 5μg/kg/Min: p = 0.4035, Mixed Models Analysis
Placebo vs CXL-1427 7μg/kg/Min: p = 0.8308, Mixed Models Analysis

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: All adverse events were reported from signed of informed consent form through 30 days post final infusion of study drug.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	1 of 12 (8.3%)	3 of 12 (25%)	0 of 12
CXL-1427 3 μg/kg/Min	3 of 6 (50%)	6 of 6 (100%)	1 of 6
CXL-1427 5 μg/kg/Min	1 of 9 (11.1%)	6 of 9 (66.7%)	0 of 9
CXL-1427 7 μg/kg/Min	3 of 12 (25%)	7 of 12 (58.3%)	0 of 12
CXL-1427 12 μg/kg/Min	1 of 7 (14.3%)	4 of 7 (57.1%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

ShiYin Foo, M.D., Ph D. study director

Cardioxyl Pharmaceuticals

35 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CXL-1427 in people with Heart Failure and Decompensated Heart Failure, run by Bristol-Myers Squibb at 35 sites in 5 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 35 inclusion and 0 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 31 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in United States, Russia, Germany, Poland, Jordan. 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 May 2019). 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?

Number of Participants With Treatment-Emergent Adverse Events (time frame: 30 days following the initiation of treatment). The study lists 4 primary outcomes in all. 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 NCT02157506.

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 31 Jul 2019.