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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Cardiorentis
Sponsor:
Collaborator:
Quintiles
Information provided by (Responsible Party):
Cardiorentis
ClinicalTrials.gov Identifier:
NCT01661634
First received: July 31, 2012
Last updated: October 1, 2014
Last verified: October 2014
  Purpose

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 Intervention Phase
Acute Decompensated Heart Failure
Drug: Ularitide
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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]

Resource links provided by NLM:


Further study details as provided by Cardiorentis:

Primary Outcome Measures:
  • Two Co-primary Efficacy Endpoints [ Time Frame: 6, 24, 48 hours post infusion through the entire duration of the trial ] [ Designated as safety issue: No ]

    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:
  • Secondary Endpoint [ Time Frame: 48 hours post infusion start ] [ Designated as safety issue: No ]
    Changes of N-terminal pro brain natriuretic peptide (NT-pro BNP) at 48 h of treatment compared to baseline.

  • Secondary Endpoint [ Time Frame: 90 days after start of study drug infusion, including patients still hospitalized at Day 30 ] [ Designated as safety issue: No ]
    All-cause mortality and cardiovascular rehospitalization

  • Secondary Endpoint [ Time Frame: 90 days after start of study drug infusion, including patients still hospitalized at Day 30 ] [ Designated as safety issue: No ]
    Cardiovascular rehospitalization


Estimated Enrollment: 2152
Study Start Date: July 2012
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
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
    • Brain natriuretic peptide (BNP) >500 pg/mL or N-terminal pro-brain natriuretic peptide (NT-pro BNP) >2000 pg/mL.
  3. Ability to start infusion of the study drug within 12 h after initial clinical assessment performed by a physician at the emergency room/hospital.
  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 ongoing IV infusions 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 <30 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:

    • Prolonged chest pain at rest, or an accelerated pattern of angina
    • 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.
    • 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 including 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 heart failure with expected survival <180 days.
  14. Any previous exposure to ularitide.
  15. Known allergy to natriuretic peptides.
  16. Participation in an investigational clinical drug trial 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01661634

Contacts
Contact: Matteo Mondellini +39 02 93922665 matteo.mondellini@quintiles.com

  Show 186 Study Locations
Sponsors and Collaborators
Cardiorentis
Quintiles
Investigators
Study Chair: Milton Packer, MD
Principal Investigator: Christopher O'Connor, MD
Principal Investigator: William F Peacock, MD
  More Information

Publications:
Responsible Party: Cardiorentis
ClinicalTrials.gov Identifier: NCT01661634     History of Changes
Other Study ID Numbers: ULA01, 2010-024249-59
Study First Received: July 31, 2012
Last Updated: October 1, 2014
Health Authority: United States: Food and Drug Administration
Czech Republic: State Institute for Drug Control
Denmark: Danish Health and Medicines Authority
Estonia: The State Agency of Medicine
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Agency for Medicines and Medical Devices
Sweden: Medical Products Agency
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Switzerland: Swissmedic
Tunisia: Office of Pharmacies and Medicines
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: National Health Surveillance Agency
Canada: Health Canada
Chile: Instituto de Salud Pública de Chile
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Turkey: General Directorate of Pharmaceuticals and Pharmacy

Keywords provided by Cardiorentis:
Acute decompensated heart failure

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases
Ularitide
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Diuretics
Natriuretic Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014