Efficacy and safety of ularitide for the treatment of acute decompensated heart failure full text view - clinical trials

1. 11/15/13 Efficacyand Safetyof Ularitide for the Treatment of Acute Decompensated Heart Failure - Full Text View - ClinicalTrials.gov
clinicaltrials.gov/ct2/show/study/NCT01661634?term=urodilatin&rank=2 1/4
This study is currently recruiting participants.
Verified August 2013 by Cardiorentis
Sponsor:
Cardiorentis
Collaborator:
Quintiles
Information provided by (Responsible Party):
Cardiorentis
ClinicalTrials.gov Identifier:
NCT01661634
First received: July 31, 2012
Last updated: August 8, 2013
Last verified: August 2013
History of Changes
Full Text View Tabular View No Study Results Posted Disclaimer How to Read a Study Record
A service of the U.S. National Institutes of Health
Trial record 2 of 3 for: urodilatin
Previous Study | Return to List | Next Study
Efficacy and Safety of Ularitide for the Treatment of Acute Decompensated Heart Failure (TRUE-AHF)
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:
MedlinePlus related topics: Heart Failure
U.S. FDA Resources
Further study details as provided by Cardiorentis:
Primary Outcome Measures:
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.
Primary Safety Endpoint [ Time Frame: 30 days after start of study drug infusion ] [ Designated as safety issue: No ]
All-cause mortality and cardiovascular rehospitalization
Secondary Outcome Measures:

2. 11/15/13 Efficacyand Safetyof Ularitide for the Treatment of Acute Decompensated Heart Failure - Full Text View - ClinicalTrials.gov
clinicaltrials.gov/ct2/show/study/NCT01661634?term=urodilatin&rank=2 2/4
Secondary Efficacy 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 Safety Endpoint [ Time Frame: 90 days after start of study drug infusion ] [ Designated as safety issue: No ]
All-cause mortality and cardiovascular rehospitalization
Secondary Safety Endpoint [ Time Frame: 90 days after start of study drug infusion ] [ Designated as safety issue: No ]
Cardiovascular mortality
Estimated Enrollment: 2152
Study Start Date: July 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: September 2014 (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 ≥110 mmHg.
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:

3. 11/15/13 Efficacyand Safetyof Ularitide for the Treatment of Acute Decompensated Heart Failure - Full Text View - ClinicalTrials.gov
clinicaltrials.gov/ct2/show/study/NCT01661634?term=urodilatin&rank=2 3/4
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
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01661634
Contacts
Contact: Matteo Mondellini +39 02 93922665 matteo.mondellini@quintiles.com
Show 144 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:
Mitrovic V, Lüss H, Nitsche K, Forssmann K, Maronde E, Fricke K, Forssmann WG, Meyer M. Effects of the renal natriuretic peptide urodilatin
(ularitide) in patients with decompensated chronic heart failure: a double-blind, placebo-controlled, ascending-dose trial. Am Heart J. 2005
Dec;150(6):1239.
Mitrovic V, Seferovic PM, Simeunovic D, Ristic AD, Miric M, Moiseyev VS, Kobalava Z, Nitsche K, Forssmann WG, Lüss H, Meyer M.
Haemodynamic and clinical effects of ularitide in decompensated heart failure. Eur Heart J. 2006 Dec;27(23):2823-32. Epub 2006 Oct 30.

4. 11/15/13 Efficacyand Safetyof Ularitide for the Treatment of Acute Decompensated Heart Failure - Full Text View - ClinicalTrials.gov
clinicaltrials.gov/ct2/show/study/NCT01661634?term=urodilatin&rank=2 4/4
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: August 8, 2013
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 Publica 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
Heart Diseases
Cardiovascular Diseases
Atrial natriuretic factor prohormone (95-126)
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Diuretics
Natriuretic Agents
Cardiovascular Agents
ClinicalTrials.gov processed this record on November 14, 2013