Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01661634
Other study ID # ULA01
Secondary ID 2010-024249-59
Status Completed
Phase Phase 3
First received
Last updated
Start date July 2012
Est. completion date March 2016

Study information

Verified date October 2018
Source Cardiorentis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


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.


Recruitment information / eligibility

Status Completed
Enrollment 2157
Est. completion date March 2016
Est. primary completion date November 2015
Accepts healthy volunteers No
Gender All
Age group 18 Years to 85 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Ularitide

Placebo


Locations

Country Name City State
n/a

Sponsors (2)

Lead Sponsor Collaborator
Cardiorentis Quintiles, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Czechia,  Estonia,  Finland,  France,  Germany,  Hungary,  Israel,  Italy,  Latvia,  Lithuania,  Netherlands,  Poland,  Romania,  Serbia,  Spain,  Switzerland,  Turkey, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Two Co-primary Efficacy Endpoints 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.
6, 24, 48 hours post infusion through the entire duration of the trial
Secondary Length of stay of index hospitalization in hours after start of study drug infusion up to 30 days
Secondary Length of stay in intensive care (intensive care unit [ICU] or critical care unit [CCU]) during the first 120 h following the start of the study drug infusion.
Secondary Number of events of persistent or worsening HF requiring an intervention from the start of the study drug infusion to 120 h.
Secondary Proportion of patients with persistent or worsening HF and requiring an intervention from the start of study drug infusion to 120 h.
Secondary Reduction in rehospitalization for heart failure within 30 days after initial hospital
Secondary Changes of N-terminal pro brain natriuretic peptide (NT-pro BNP) 48 h of treatment compared to baseline.
Secondary 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) for the first 120 h following the start of the drug infusion.
Secondary Change in serum creatinine from baseline through 72 h.
Secondary 180 days after start of study drug infusion, including patients still hospitalized at Day 30. All-cause mortality and cardiovascular rehospitalization
See also
  Status Clinical Trial Phase
Completed NCT04049045 - Effects of Empagliflozin on Diuresis and Renal Function in Patients With Acute Decompensated Heart Failure Phase 2
Active, not recruiting NCT05100836 - SURPASS Impella 5.5 Study
Recruiting NCT02898181 - Low Level Tragus Stimulation in Acute Decompensated Heart Failure N/A
Completed NCT02823626 - High-dose Aldosterone Antagonist for Acute Decompensated Heart Failure
Completed NCT02248831 - Evaluation of Cardiopulmonary Diseases by Ultrasound N/A
Completed NCT02196038 - A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients N/A
Completed NCT00693745 - Neutrophil Gelatinase-Associated Lipcalin (NGAL) Evaluation Along With B-Type Natriuretic Peptide in Acutely Decompensated HF N/A
Not yet recruiting NCT04391231 - HEMolysis in a Percutaneous Axial Flow LVAD, Effects of Pentoxifylline in a Randomized Controlled Trial Phase 4
Recruiting NCT05206422 - DORAYA-HF Early Feasibility Study N/A
Recruiting NCT01960218 - Gas Exchange for Predicting Hospital Heart Failure Readmissions N/A
Terminated NCT00904488 - Oral Metolazone and Intermittent Intravenous Furosemide Versus Continuous Infusion Furosemide in Acute Heart Failure Phase 4
Terminated NCT02620384 - Metolazone As Early Add On Therapy For Acute Decompensated Heart Failure (MELT-HF)--A Single Center Pilot Study. Phase 3
Completed NCT04318093 - Study of the Safety of BMS-986259 in Participants With Post-Acute Decompensated Heart Failure Phase 2
Recruiting NCT06161649 - Mobile Education System to Improve Disease Knowledge, Self-efficacy and Quality of Life in Patients With Heart Failure N/A
Completed NCT02289508 - Role of USCOM in Adult Patients With Heart Failure N/A
Terminated NCT01457053 - Assessment of Coronary Flow Reserve in Heart Failure Patients After Ultrafiltration Versus Diuretics N/A
Completed NCT04877652 - DR REGISTRY: Prospective Observational Study of ADHF Patients With Insufficient Response to Diuretics
Completed NCT03505788 - Acetazolamide in Decompensated Heart Failure With Volume OveRload (ADVOR) Phase 4
Completed NCT03146754 - A Study to Evaluate Lung Ultrasound as a Method to Measure Changes in Extravascular Lung Water Induced by Positional Changes (LUPE) N/A
Not yet recruiting NCT06414759 - Efficacy and Safety of Combination Diuretic Therapy in Patients With Acute Decompensated Heart Failure and Volume Overload Phase 4