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Acute Decompensated Heart FailurePhase 3TRUE-AHFNCT01661634

Efficacy and Safety of Ularitide for the Treatment of Acute Decompensated Heart Failure

A Phase 3 study testing Ularitide in people with Acute Decompensated Heart Failure, run by Cardiorentis at 163 sites in 22 countries.

Completed

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

Official record
Search all trials

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). Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Acute Decompensated Heart Failure
What is being tested?
Ularitide
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
2,157 participants
Where
163 sitesin 22 countries
Study dates
Jul 2012to Mar 2016
Phase
Phase 3
Are there results?
None posted in the registry

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

  • Males and females aged 18 to 85 years.
  • 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.
Show all 11Show fewer
  • Ability to start infusion of the study drug within 12 h after initial clinical assessment.
  • Ability to reliably carry out self-assessment of symptoms.
  • Systolic blood pressure ≥116 mmHg and ≤180 mmHg at the time of randomization.
  • 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.
  • 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).

Who cannot join

  • Known active myocarditis, obstructive hypertrophic cardiomyopathy, congenital heart disease, restrictive cardiomyopathy, constrictive pericarditis, uncorrected clinically significant primary valvular disease.
  • Treatment with dobutamine at a dose >5 μg/kg/min or use of drugs for support of BP at the time of randomization.
  • Treatment with levosimendan, milrinone, or any other phosphodiesterase inhibitor within 7 days before randomization.
  • Treatment with nesiritide within 30 days before randomization.
  • Creatinine clearance <25 mL/min/1.73m² (as measured by the MDRD formula) at the time of screening.
  • Planned coronary revascularization procedure (percutaneous coronary intervention or coronary artery bypass grafting) within 5 days of randomization.
Show all 26Show fewer
  • 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.
  • Clinically suspected acute mechanical cause of ADHF (e.g., papillary muscular rupture). The diagnosis need not be confirmed by imaging or cardiac catheterization.
  • Anemia (hemoglobin <9 g/dL or a hematocrit <25%).
  • Known vasculitis, active infective endocarditis, or suspected infections, e.g., pneumonia, acute hepatitis, systemic inflammatory response syndrome, or sepsis.
  • Body temperature ≥38°C just prior to randomization.
  • 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.
  • Terminal illness other than congestive HF with expected survival <180 days.
  • Any previous exposure to ularitide.
  • Known allergy to natriuretic peptides.
  • Participation in an investigational clinical drug study within 30 days prior to randomization.
  • Current drug abuse or chronic alcoholism sufficient to impair participation and compliance to the study protocol.
  • Women who are breast-feeding.
  • 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.
  • Any condition that, in the Investigator's opinion, makes the patient unsuitable for study participation.
  • Legal incapacity or limited legal capacity.
  • Patients requiring mechanical circulatory support.
  • Patients with severe hepatic impairment.

Trial locations and contacts

163 sites in 22 countries.

163 sites in 22 countries

United States39 sites

  • Study site

    Alexandria, Louisiana, 71303

  • Study site

    Austin, Texas, 78758

  • Study site

    Brooklyn, New York, 11203

  • Study site

    Charleston, South Carolina, 29425

  • Study site

    Charlottesville, Virginia, 22908

  • Study site

    Chattanooga, Tennessee, 37403

  • Study site

    Cincinnati, Ohio, 45219

  • Study site

    Columbus, Ohio, 43210

  • Study site

    Dallas, Texas, 75390

  • Study site

    Detroit, Michigan, 48201

  • Study site

    Detroit, Michigan, 48202

  • Study site

    Detroit, Michigan, 48235

  • Study site

    Fort Worth, Texas, 76104

  • Study site

    Houston, Texas, 77030

  • Study site

    Huntsville, Alabama, 35801

  • Study site

    Jacksonville, Florida, 32216

  • Study site

    Kansas City, Kansas, 66160

  • Study site

    Lawrenceville, Georgia, 30046

  • Study site

    Lincoln, Nebraska, 68526

  • Study site

    Littleton, Colorado, 80120

  • Study site

    Middletown, Ohio, 45005

  • Study site

    Midlothian, Virginia, 23114

  • Study site

    Minneapolis, Minnesota, 55415

  • Study site

    Montgomery, Alabama, 36106

  • Study site

    Nashville, Tennessee, 37232

  • Study site

    Newark, New Jersey, 07107

  • Study site

    Norfolk, Virginia, 23507

  • Study site

    Peoria, Illinois, 61606

  • Study site

    Philadelphia, Pennsylvania, 19141

  • Study site

    Rockford, Illinois, 61107

  • Study site

    Royal Oak, Michigan, 48073

  • Study site

    Sacramento, California, 95817

  • Study site

    Salem, Virginia, 24153

  • Study site

    St Louis, Missouri, 63110

  • Study site

    The Bronx, New York, 10467

  • Study site

    Toledo, Ohio, 43614

  • Study site

    Trumbull, Connecticut, 06611

  • Study site

    Washington D.C., District of Columbia, 20422

  • Study site

    Worcester, Massachusetts, 01655

Other trials in United States

Argentina16 sites

  • Study site

    Ciudad Autonoma, Buenos Aires, 1180

  • Study site

    Córdoba, Córdoba Province, X5008KKF

  • Study site

    Córdoba, 5000

  • Study site

    Córdoba, 5016

  • Study site

    Córdoba, X5000JHQ

  • Study site

    Córdoba, X5002AOQ

  • Study site

    Córdoba, X5004BAL

  • Study site

    Coronel Suárez, Buenos Aires, B7540GHD

  • Study site

    Corrientes, W3400AMZ

  • Study site

    La Plata, Buenos Aires, 1900

  • Study site

    Rosario, Santa Fe Province, 2000

  • Study site

    San Miguel de Tucumán, Tucumán Province, 4000

  • Study site

    San Miguel de Tucumán, T4000NIL

  • Study site

    San Vicente, Córdoba Province, 5006

  • Study site

    Santa Fe, S3000EOZ

  • Study site

    Santa Fe, S3000FUJ

Other trials in Argentina

Italy14 sites

  • Study site

    Alessandria, 15100

  • Study site

    Bari, 70124

  • Study site

    Bologna, 40138

  • Study site

    Como, 22020

  • Study site

    Genova, 16132

  • Study site

    Legnano, Milano, 20025

  • Study site

    Milan, 20138

  • Study site

    Milan, 20162

  • Study site

    Naples, 80131

  • Study site

    Novara, 28100

  • Study site

    Roma, 00189

  • Study site

    Rozzano, Milano, 20089

  • Study site

    San Fermo della Battaglia, Como, 22020

  • Study site

    Varese, 21100

Other trials in Italy

Czechia11 sites

  • Study site

    Brno, 625 00

  • Study site

    Brno, 65691

  • Study site

    Frýdek-Místek, 73818

  • Study site

    Hradec Králové, 50012

  • Study site

    Olomouc, 775 20

  • Study site

    Prague, 100 34

  • Study site

    Prague, 128 08

  • Study site

    Prague, 140 00

  • Study site

    Prague, 150 06

  • Study site

    Prague, 150 30

  • Study site

    Znojmo, 669 02

Other trials in Czechia

Germany11 sites

  • Study site

    Bad Nauheim, Hesse, 61231

  • Study site

    Berlin, 10249

  • Study site

    Berlin, 12351

  • Study site

    Berlin, 13353

  • Study site

    Bochum, North Rhine-Westphalia, 44787

  • Study site

    Erfurt, Thuringia, 99089

  • Study site

    Greifswald, Mecklenburg-Vorpommern, 17475

  • Study site

    Groß-Umstadt, Hesse, 64823

  • Study site

    Jena, Thuringia, 07743

  • Study site

    Langen, Hesse, 63225

  • Study site

    Nuremberg, Bavaria, 90419

Other trials in Germany

Spain10 sites

  • Study site

    Alicante, 03010

  • Study site

    Aranjuez, Madrid, 28300

  • Study site

    Barcelona, 08025

  • Study site

    Barcelona, 08036

  • Study site

    L'Hospitalet de Llobregat, Barcelona, 08907

  • Study site

    Madrid, 28040

  • Study site

    Majadahonda, Madrid, 28222

  • Study site

    Majadahonda, Madrid, 28822

  • Study site

    Sant Joan Despí, Barcelona, 08970

  • Study site

    Santiago de Compostela, La Coruña, 15706

Other trials in Spain

Israel8 sites

  • Study site

    Afula, 1834111

  • Study site

    Ashkelon, 7830604

  • Study site

    Hadera, 38100

  • Study site

    Holon, 5810001

  • Study site

    Kfar Saba, 4428164

  • Study site

    Nahariya, 2210001

  • Study site

    Nazareth, 1610001

  • Study site

    Safed, 13100

Other trials in Israel

Serbia7 sites

  • Study site

    Belgrade, 11000

  • Study site

    Belgrade, 11040

  • Study site

    Belgrade, 11080

  • Study site

    Kamenitz, 21204

  • Study site

    Niš, 18000

  • Study site

    Niška Banja, 18205

  • Study site

    Zemun, 11080

Other trials in Serbia

France6 sites

  • Study site

    Bayonne, Pyrenees Atlantiques, 64100

  • Study site

    Besançon, Doubs, 25030

  • Study site

    Bron, Rhone, 69677

  • Study site

    Paris, Paris, 75475

  • Study site

    Poitiers, Vienne, 86000

  • Study site

    Toulouse, Haute Garonne, 31059

Other trials in France

Netherlands6 sites

  • Study site

    Beverwijk, 1942 LE

  • Study site

    Ede, 6716 RP

  • Study site

    Gorinchem, 4204 AA

  • Study site

    Groningen, 9713 GZ

  • Study site

    Leiderdorp, 2353 GA

  • Study site

    Sneek, 8601 ZK

Other trials in Netherlands

Poland6 sites

  • Study site

    Krakow, 31-121

  • Study site

    Krakow, 31-202

  • Study site

    Lodz, 91-347

  • Study site

    Warsaw, 03-242

  • Study site

    Warsaw, 04-628

  • Study site

    Wroclaw, 50-981

Other trials in Poland

Brazil5 sites

  • Study site

    Campinas, São Paulo, 13060-904

  • Study site

    Goiânia, Goiás, 74605-020

  • Study site

    Porto Alegre, Rio Grande do Sul, 90035-003

  • Study site

    São José do Rio Preto, São Paulo, 15090-000

  • Study site

    São Paulo, São Paulo, 05403-000

Other trials in Brazil

Romania4 sites

  • Study site

    Bucharest, 021659

  • Study site

    Bucharest, 050098

  • Study site

    Iași, 700503

  • Study site

    Oradea, 410169

Other trials in Romania

Turkey (Türkiye)4 sites

  • Study site

    Eskişehir, 26480

  • Study site

    Istanbul, 34662

  • Study site

    Kocaeli, 41300

  • Study site

    Sivas, 58140

Other trials in Turkey (Türkiye)

Canada3 sites

  • Study site

    Halifax, Nova Scotia, B3H 2Y9

  • Study site

    Montreal, Quebec, H1T1C8

  • Study site

    Montreal, Quebec, H2W 1T8

Other trials in Canada

Lithuania3 sites

  • Study site

    Kaunas, 45130

  • Study site

    Kaunas, 50009

  • Study site

    Vilnius, 08661

Other trials in Lithuania

Switzerland3 sites

  • Study site

    Basel, 4031

  • Study site

    Lugano, 6900

  • Study site

    Zurich, 8091

Other trials in Switzerland

Belgium2 sites

  • Study site

    Aalst, 9300

  • Study site

    Kortrijk, 8500

Other trials in Belgium

Estonia2 sites

  • Study site

    Tallinn, 10138

  • Study site

    Tallinn, 13419

Other trials in Estonia

Finland1 site

  • Study site

    Espoo, 02740

Other trials in Finland

Hungary1 site

  • Study site

    Debrecen, 4032

Other trials in Hungary

Latvia1 site

  • Study site

    Riga, LV1002

Other trials in Latvia

About this study

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]

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).

Read the 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.

Being tested
Ularitide, Placebo
Keywords
Acute decompensated heart failure

What participants receive

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

  • UlaritideDrug

  • PlaceboDrug

Study groups in NCT01661634
Study groupRoleWhat they receive
UlaritideExperimentalUlaritide, lyophilizate for i.v. infusion, 15 ng/kg BW/min, for 48 hours
Receives: Drug: Ularitide
PlaceboPlacebo comparatorPlacebo lyophilizate for i.v. infusion
Receives: Drug: Placebo

What is being measured

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

  1. 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.

    Measured: 6, 24, 48 hours post infusion through the entire duration of the trial

Secondary outcomes (9)

  1. Length of stay of index hospitalization in hours after start of study drug infusion

    Measured: up to 30 days

  2. Length of stay in intensive care (intensive care unit [ICU] or critical care unit [CCU])

    Measured: 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

    Measured: from the start of the study drug infusion to 120 h.

  4. Proportion of patients with persistent or worsening HF and requiring an intervention

    Measured: from the start of study drug infusion to 120 h.

  5. Reduction in rehospitalization for heart failure

    Measured: within 30 days after initial hospital

  6. Changes of N-terminal pro brain natriuretic peptide (NT-pro BNP)

    Measured: 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)

    Measured: for the first 120 h following the start of the drug infusion.

  8. Change in serum creatinine

    Measured: from baseline through 72 h.

  9. 180 days after start of study drug infusion, including patients still hospitalized at Day 30.

    Measured: All-cause mortality and cardiovascular rehospitalization

Timeline

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

  1. First posted9 Aug 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionNov 2015
  4. Study completionMar 2016

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
2,157 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01661634
Sponsor's protocol ID
ULA01
Other IDs
2010-024249-59
Acronym
TRUE-AHF
Status last verified
Oct 2018
First submitted
31 Jul 2012
Last updated
23 Oct 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • Mitrovic V, Luss 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. doi: 10.1016/j.ahj.2005.01.022.

    PubMed 16338265

  • Mitrovic V, Seferovic PM, Simeunovic D, Ristic AD, Miric M, Moiseyev VS, Kobalava Z, Nitsche K, Forssmann WG, Luss H, Meyer M. Haemodynamic and clinical effects of ularitide in decompensated heart failure. Eur Heart J. 2006 Dec;27(23):2823-32. doi: 10.1093/eurheartj/ehl337. Epub 2006 Oct 30.

    PubMed 17074775

  • Packer M, O'Connor C, McMurray JJV, Wittes J, Abraham WT, Anker SD, Dickstein K, Filippatos G, Holcomb R, Krum H, Maggioni AP, Mebazaa A, Peacock WF, Petrie MC, Ponikowski P, Ruschitzka F, van Veldhuisen DJ, Kowarski LS, Schactman M, Holzmeister J; TRUE-AHF Investigators. Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure. N Engl J Med. 2017 May 18;376(20):1956-1964. doi: 10.1056/NEJMoa1601895. Epub 2017 Apr 12.

    PubMed 28402745

  • Packer M, Holcomb R, Abraham WT, Anker S, Dickstein K, Filippatos G, Krum H, Maggioni AP, McMurray JJV, Mebazaa A, O'Connor C, Peacock F, Ponikowski P, Ruschitzka F, van Veldhuisen DJ, Holzmeister J; TRUE-AHF Investigators and Committees. Rationale for and design of the TRUE-AHF trial: the effects of ularitide on the short-term clinical course and long-term mortality of patients with acute heart failure. Eur J Heart Fail. 2017 May;19(5):673-681. doi: 10.1002/ejhf.698. Epub 2016 Nov 13.

    PubMed 27862700

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ularitide in people with Acute Decompensated Heart Failure, run by Cardiorentis at 163 sites in 22 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 11 inclusion and 26 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 23 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 163 sites in United States, Argentina, Italy, Czechia, Germany and 17 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Two Co-primary Efficacy Endpoints (time frame: 6, 24, 48 hours post infusion through the entire duration of the trial). 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 NCT01661634, which also lists 4 linked publications.

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 23 Oct 2018.

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