Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of Ularitide for the Treatment of Acute Decompensated Heart Failure (TRUE-AHF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01661634
Recruitment Status : Completed
First Posted : August 9, 2012
Last Update Posted : October 23, 2018
Sponsor:
Collaborator:
Quintiles, Inc.
Information provided by (Responsible Party):
Cardiorentis

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of a continuous intravenous (IV) ularitide infusion on the clinical status and outcome of patients with acute decompensated heart failure (ADHF).

Condition or disease Intervention/treatment Phase
Acute Decompensated Heart Failure Drug: Ularitide Drug: Placebo Phase 3

Detailed Description:

The objective of the TRUE-AHF study is to evaluate the effect of a 48-h continuous IV infusion of ularitide (15 ng/kg/min) versus placebo on the clinical status of patients with acute decompensated heart failure (ADHF).

The study drug will be administered in addition to the standard treatment. The nature of standard therapy will be carried out according to the clinical judgment of the Investigator and may include vasodilator, inotropic, and diuretic drugs, as clinically indicated.

There are two co-primary endpoints for this study. Co-primary endpoint 1 will be a hierarchical clinical composite variable that includes a patient-centered assessment of clinical progress, an assessment of lack of improvement or worsening of HF requiring a pre-specified intervention, and death.

The endpoint is intended to mimic the assessment that would be carried out by a physician caring for the patient. If, during the 48 h infusion, a patient's clinical course deteriorates because he/she dies, fails to improve or develops worsening HF requiring a pre-specified intervention or if the patient considers his/her general clinical status as moderately or markedly worse, the patient will be considered to be "worse". If the patient considers his/her general clinical status as moderately or markedly improved and if such improvement is sustained without fulfilling the criteria for "worse" throughout the 48-h infusion (from 0 h to 48 h), the patient will be considered to be "improved". If the patient is neither improved nor worse, the patient's clinical status will be considered to be "unchanged".

Co-primary efficacy endpoint 2 evaluates freedom from cardiovascular mortality during follow up after randomization, for the entire duration of the trial.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2157 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Ularitide (Urodilatin) Intravenous Infusion in Patients Suffering From Acute Decompensated Heart Failure [TRUE-AHF]
Study Start Date : July 2012
Actual Primary Completion Date : November 2015
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Experimental: Ularitide
Ularitide, lyophilizate for i.v. infusion, 15 ng/kg BW/min, for 48 hours
Drug: Ularitide
Placebo Comparator: Placebo
Placebo lyophilizate for i.v. infusion
Drug: Placebo



Primary Outcome Measures :
  1. Two Co-primary Efficacy Endpoints [ Time Frame: 6, 24, 48 hours post infusion through the entire duration of the trial ]

    Improvement in a hierarchical clinical composite comprised of elements associated with: patient global assessment using a 7-point scale of symptomatic improvement, lack of improvement, or worsening; persistent or worsening heart failure (HF) requiring an intervention (initiation or intensification of IV therapy, circulatory or ventilatory mechanical support, surgical intervention, ultrafiltration, hemofiltration or dialysis); and all-cause mortality. Assessment of the clinical composite will be performed at 6 hour (h), 24 h and 48 h after start of IV ularitide infusion

    Freedom from cardiovascular mortality during follow up after randomization, for the entire duration of the trial.



Secondary Outcome Measures :
  1. Length of stay of index hospitalization in hours after start of study drug infusion [ Time Frame: up to 30 days ]
  2. Length of stay in intensive care (intensive care unit [ICU] or critical care unit [CCU]) [ Time Frame: during the first 120 h following the start of the study drug infusion. ]
  3. Number of events of persistent or worsening HF requiring an intervention [ Time Frame: from the start of the study drug infusion to 120 h. ]
  4. Proportion of patients with persistent or worsening HF and requiring an intervention [ Time Frame: from the start of study drug infusion to 120 h. ]
  5. Reduction in rehospitalization for heart failure [ Time Frame: within 30 days after initial hospital ]
  6. Changes of N-terminal pro brain natriuretic peptide (NT-pro BNP) [ Time Frame: 48 h of treatment compared to baseline. ]
  7. Time to completion of last dose of any IV drugs that can be used for the treatment of HF (e.g., diuretics, vasodilators, or positive inotropic agents) [ Time Frame: for the first 120 h following the start of the drug infusion. ]
  8. Change in serum creatinine [ Time Frame: from baseline through 72 h. ]
  9. 180 days after start of study drug infusion, including patients still hospitalized at Day 30. [ Time Frame: All-cause mortality and cardiovascular rehospitalization ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males and females aged 18 to 85 years.
  2. Unplanned hospitalization or emergency department visit for ADHF. Acute HF is defined as including all of the following:

    • Dyspnea at rest in a recumbent sitting position (30 to 45 degrees), which has worsened within the past week;
    • Radiological evidence of HF on a chest X-ray (if an appropriate chest;
    • computerized tomography scan is done; the X-ray need not be performed);
    • Brain natriuretic peptide (BNP) >500 pg/mL or NT-pro BNP >2000 pg/mL.
  3. Ability to start infusion of the study drug within 12 h after initial clinical assessment.
  4. Ability to reliably carry out self-assessment of symptoms.
  5. Systolic blood pressure ≥116 mmHg and ≤180 mmHg at the time of randomization.
  6. Persisting dyspnea at rest despite standard background therapy for ADHF (as determined by the Investigator) which must include IV furosemide (or equivalent diuretic) at ≥40 mg (or its equivalent) at any time after start of emergency services (ambulance, emergency department, or hospital). At the time of randomization, the patient must still be symptomatic. In addition, the patient should not have received an IV bolus of a diuretic for at least 2 h prior to randomization, and the infusion rates of all ongoing IV infusions of medications to treat HF must not have been increased or decreased for at least 2 h prior to randomization.
  7. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local privacy regulations).

Exclusion Criteria:

  1. Known active myocarditis, obstructive hypertrophic cardiomyopathy, congenital heart disease, restrictive cardiomyopathy, constrictive pericarditis, uncorrected clinically significant primary valvular disease.
  2. Treatment with dobutamine at a dose >5 μg/kg/min or use of drugs for support of BP at the time of randomization.
  3. Treatment with levosimendan, milrinone, or any other phosphodiesterase inhibitor within 7 days before randomization.
  4. Treatment with nesiritide within 30 days before randomization.
  5. Creatinine clearance <25 mL/min/1.73m² (as measured by the MDRD formula) at the time of screening.
  6. Planned coronary revascularization procedure (percutaneous coronary intervention or coronary artery bypass grafting) within 5 days of randomization.
  7. Clinical diagnosis of acute coronary syndrome meeting any 2 of the following 3 criteria:

    1. Prolonged chest pain at rest, or an accelerated pattern of angina
    2. Electrocardiogram changes indicative of ischemia or myocardial injury defined as: a new ST elevation at the J point of two anatomically contiguous leads with the cut-off points: ≥0.2 mV in men ≥40 years (>0.25 mV in men <40 years) or ≥0.15 mV in women in leads V2-V3 and/or ≥0.1 mV in other leads; or ST depression and T wave changes. New horizontal or down sloping ST depression ≥0.05 mV in two contiguous leads; and/or new T inversion ≥0.3 mV in two contiguous leads.
    3. Serum troponin >3 times upper limit of normal.
  8. Clinically suspected acute mechanical cause of ADHF (e.g., papillary muscular rupture). The diagnosis need not be confirmed by imaging or cardiac catheterization.
  9. Anemia (hemoglobin <9 g/dL or a hematocrit <25%).
  10. Known vasculitis, active infective endocarditis, or suspected infections, e.g., pneumonia, acute hepatitis, systemic inflammatory response syndrome, or sepsis.
  11. Body temperature ≥38°C just prior to randomization.
  12. Acute or chronic respiratory disorder (e.g., severe chronic obstructive pulmonary disease) or primary pulmonary hypertension sufficient to cause dyspnea at rest, which may interfere with the ability to interpret dyspnea assessments or hemodynamic measurements.
  13. Terminal illness other than congestive HF with expected survival <180 days.
  14. Any previous exposure to ularitide.
  15. Known allergy to natriuretic peptides.
  16. Participation in an investigational clinical drug study within 30 days prior to randomization.
  17. Current drug abuse or chronic alcoholism sufficient to impair participation and compliance to the study protocol.
  18. Women who are breast-feeding.
  19. Women of child-bearing potential (i.e., pre-menopausal women) without documentation of a negative urine/blood pregnancy assay within 12 h prior to randomization.
  20. Any condition that, in the Investigator's opinion, makes the patient unsuitable for study participation.
  21. Legal incapacity or limited legal capacity.
  22. Patients requiring mechanical circulatory support.
  23. Patients with severe hepatic impairment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01661634


  Hide Study Locations
Locations
Layout table for location information
United States, Alabama
Huntsville, Alabama, United States, 35801
Montgomery, Alabama, United States, 36106
United States, California
Sacramento, California, United States, 95817
United States, Colorado
Littleton, Colorado, United States, 80120
United States, Connecticut
Trumbull, Connecticut, United States, 06611
United States, District of Columbia
Washington, District of Columbia, United States, 20422
United States, Florida
Jacksonville, Florida, United States, 32216
United States, Georgia
Lawrenceville, Georgia, United States, 30046
United States, Illinois
Peoria, Illinois, United States, 61606
Rockford, Illinois, United States, 61107
United States, Kansas
Kansas City, Kansas, United States, 66160
United States, Louisiana
Alexandria, Louisiana, United States, 71303
United States, Massachusetts
Worcester, Massachusetts, United States, 01655
United States, Michigan
Detroit, Michigan, United States, 48201
Detroit, Michigan, United States, 48202
Detroit, Michigan, United States, 48235
Royal Oak, Michigan, United States, 48073
United States, Minnesota
Minneapolis, Minnesota, United States, 55415
United States, Missouri
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Lincoln, Nebraska, United States, 68526
United States, New Jersey
Newark, New Jersey, United States, 07107
United States, New York
Bronx, New York, United States, 10467
Brooklyn, New York, United States, 11203
United States, Ohio
Cincinnati, Ohio, United States, 45219
Columbus, Ohio, United States, 43210
Middletown, Ohio, United States, 45005
Toledo, Ohio, United States, 43614
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19141
United States, South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Chattanooga, Tennessee, United States, 37403
Nashville, Tennessee, United States, 37232
United States, Texas
Austin, Texas, United States, 78758
Dallas, Texas, United States, 75390
Fort Worth, Texas, United States, 76104
Houston, Texas, United States, 77030
United States, Virginia
Charlottesville, Virginia, United States, 22908
Midlothian, Virginia, United States, 23114
Norfolk, Virginia, United States, 23507
Salem, Virginia, United States, 24153
Argentina
Ciudad Autonoma, Buenos Aires, Argentina, 1180
Coronel Suarez, Buenos Aires, Argentina, B7540GHD
La Plata, Buenos Aires, Argentina, 1900
Córdoba, Cordoba, Argentina, X5008KKF
San Vicente, Cordoba, Argentina, 5006
Rosario, Santa Fe, Argentina, 2000
San Miguel de Tucuman, Tucuman, Argentina, 4000
Cordoba, Argentina, 5000
Cordoba, Argentina, 5016
Cordoba, Argentina, X5000JHQ
Cordoba, Argentina, X5002AOQ
Cordoba, Argentina, X5004BAL
Corrientes, Argentina, W3400AMZ
San Miguel de Tucuman, Argentina, T4000NIL
Santa Fe, Argentina, S3000EOZ
Santa Fe, Argentina, S3000FUJ
Belgium
Aalst, Belgium, 9300
Kortrijk, Belgium, 8500
Brazil
Goiânia, Goiás, Brazil, 74605-020
Porto Alegre, Rio Grande Do Sul, Brazil, 90035-003
Campinas, Sao Paulo, Brazil, 13060-904
São José do Rio Preto, Sao Paulo, Brazil, 15090-000
São Paulo, Sao Paulo, Brazil, 05403-000
Canada, Nova Scotia
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Quebec
Montreal, Quebec, Canada, H2W 1T8
Montréal, Quebec, Canada, H1T1C8
Czechia
Brno, Czechia, 625 00
Brno, Czechia, 65691
Frydek-Mistek, Czechia, 73818
Hradec Kralove, Czechia, 50012
Olomouc, Czechia, 775 20
Praha 10, Czechia, 100 34
Praha 2, Czechia, 128 08
Praha 4, Czechia, 140 00
Praha 5, Czechia, 150 06
Praha 5, Czechia, 150 30
Znojmo, Czechia, 669 02
Estonia
Tallinn, Estonia, 10138
Tallinn, Estonia, 13419
Finland
Espoo, Finland, 02740
France
Besançon Cedex, Doubs, France, 25030
Toulouse Cedex 9, Haute Garonne, France, 31059
Paris cedex 10, Paris, France, 75475
Bayonne, Pyrenees Atlantiques, France, 64100
Bron cedex, Rhone, France, 69677
Poitiers, Vienne, France, 86000
Germany
Nuernberg, Bayern, Germany, 90419
Bad Nauheim, Hessen, Germany, 61231
Gross-Umstadt, Hessen, Germany, 64823
Langen, Hessen, Germany, 63225
Greifswald, Mecklenburg Vorpommern, Germany, 17475
Bochum, Nordrhein Westfalen, Germany, 44787
Erfurt, Thueringen, Germany, 99089
Jena, Thueringen, Germany, 07743
Berlin, Germany, 10249
Berlin, Germany, 12351
Berlin, Germany, 13353
Hungary
Debrecen, Hungary, 4032
Israel
Afula, Israel, 1834111
Ashkelon, Israel, 7830604
Hadera, Israel, 38100
Holon, Israel, 5810001
Kfar-Saba, Israel, 4428164
Nahariya, Israel, 2210001
Nazareth, Israel, 1610001
Safed, Israel, 13100
Italy
San Fermo della Battaglia, Como, Italy, 22020
Legnano, Milano, Italy, 20025
Rozzano, Milano, Italy, 20089
Alessandria, Italy, 15100
Bari, Italy, 70124
Bologna, Italy, 40138
Como, Italy, 22020
Genova, Italy, 16132
Milano, Italy, 20138
Milano, Italy, 20162
Napoli, Italy, 80131
Novara, Italy, 28100
Roma, Italy, 00189
Varese, Italy, 21100
Latvia
Riga, Latvia, LV1002
Lithuania
Kaunas, Lithuania, 45130
Kaunas, Lithuania, 50009
Vilnius, Lithuania, 08661
Netherlands
Beverwijk, Netherlands, 1942 LE
Ede, Netherlands, 6716 RP
Gorinchem, Netherlands, 4204 AA
Groningen, Netherlands, 9713 GZ
Leiderdorp, Netherlands, 2353 GA
Sneek, Netherlands, 8601 ZK
Poland
Krakow, Poland, 31-121
Krakow, Poland, 31-202
Lodz, Poland, 91-347
Warszawa, Poland, 03-242
Warszawa, Poland, 04-628
Wroclaw, Poland, 50-981
Romania
Bucuresti, Romania, 021659
Bucuresti, Romania, 050098
Iasi, Romania, 700503
Oradea, Romania, 410169
Serbia
Belgrade, Serbia, 11000
Belgrade, Serbia, 11040
Belgrade, Serbia, 11080
Niska Banja, Serbia, 18205
Nis, Serbia, 18000
Sremska Kamenica, Serbia, 21204
Zemun, Serbia, 11080
Spain
L'Hospitalet de Llobregat, Barcelona, Spain, 08907
Sant Joan Despí, Barcelona, Spain, 08970
Santiago de Compostela, La Coruña, Spain, 15706
Aranjuez, Madrid, Spain, 28300
Majadahonda, Madrid, Spain, 28222
Majadahonda, Madrid, Spain, 28822
Alicante, Spain, 03010
Barcelona, Spain, 08025
Barcelona, Spain, 08036
Madrid, Spain, 28040
Switzerland
Basel, Switzerland, 4031
Lugano, Switzerland, 6900
Zuerich, Switzerland, 8091
Turkey
Eskisehir, Turkey, 26480
Istanbul, Turkey, 34662
Kocaeli, Turkey, 41300
Sivas, Turkey, 58140
Sponsors and Collaborators
Cardiorentis
Quintiles, Inc.
Investigators
Layout table for investigator information
Study Chair: Milton Packer, MD
Principal Investigator: Christopher O'Connor, MD
Principal Investigator: William F. Peacock, MD

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Cardiorentis
ClinicalTrials.gov Identifier: NCT01661634     History of Changes
Other Study ID Numbers: ULA01
2010-024249-59 ( EudraCT Number )
First Posted: August 9, 2012    Key Record Dates
Last Update Posted: October 23, 2018
Last Verified: October 2018

Keywords provided by Cardiorentis:
Acute decompensated heart failure

Additional relevant MeSH terms:
Layout table for MeSH terms
Heart Failure
Heart Diseases
Cardiovascular Diseases
Ularitide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Diuretics
Natriuretic Agents