Acute Heart FailurePhase 3VERITAS 1NCT00525707
Tezosentan in Acute Heart Failure
A Phase 3 study testing tezosentan in people with Acute Heart Failure and Acute Decompensation of Chronic Heart Failure, run by Idorsia Pharmaceuticals Ltd. at 35 sites in 10 countries.
Trial summary
The randomized patients with acute heart failure will be stratified based on the presence or absence of a Swan-Ganz catheter and assigned to receive either tezosentan 5 mg/h for the first 30 minutes and 1 mg/h thereafter or matching placebo in a 1:1 manner. The duration of the treatment is 24 hours up to 72 hours. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Heart Failure, Acute Decompensation of Chronic Heart Failure, New Onset of Heart Failure
- What is being tested?
- tezosentan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 735 participants
- Where
- 35 sitesin 10 countries
- Study dates
- Apr 2003to Jan 2005
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients 18 years of age or older.
- Male or non-breast-feeding, non-pregnant female (only females who are post menopausal, surgically sterile or practicing a reliable method of contraception).
- Acute heart failure (ischemic or non-ischemic).
- Randomization within 24 hours of hospitalization (including emergency room stay) for acute heart failure.
- Dyspnea at rest as assessed by the patient and breathing rate ³ 24/min (measured during 60 seconds).
- At least two out of the following four criteria: · elevated BNP or N terminal pro-BNP (more than three times the upper limit of normal for the site) in patients not treated with nesiritide,· clinical evidence of pulmonary congestion/edema (e.g., rales or crackles more than a third above bases),· evidence of pulmonary congestion on chest X-ray, · left ventricular systolic dysfunction (EF < 40% or wall motion index £ 1.2 within 12 months prior to randomization).
- Patients in need of i.v. therapy for acute heart failure and who have received at least one dose of i.v. diuretic within 24 hours prior to study drug initiation (last bolus dose must have been more than 2 hours prior to study drug initiation).
- Written informed consent.
Who cannot join
- Criteria only for patients hemodynamically monitored:
- Baseline cardiac index > 2.5 l/min/m2 and/or PCWP < 20 mmHg within 6 hours prior to study drug initiation.
- Criteria for all patients:
- Patients not receiving i.v. vasodilators (e.g., nitrates, nitroprusside, nesiritide) at baseline: supine systolic blood pressure < 100 mmHg. Patients receiving i.v. vasodilators (e.g., nitrates, nitroprusside, nesiritide) at baseline: supine systolic blood pressure < 120 mmHg.
- Cardiogenic shock within the last 48 hours or evidence of volume depletion.
- Ongoing myocardial ischaemia, coronary revascularisation procedure (PCI or CABG) during current admission or planned revascularisation.
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- ST-segment elevation myocardial infarction or administration of thrombolytic therapy.
- Baseline creatinine ≥ 2.5 mg/dl (221 mmol/l).
- Baseline hemoglobin < 10 g/dl or a hematocrit < 30%.
- Hemodialysis, ultrafiltration or peritoneal dialysis within the last 7 days.
- Heart failure due to active myocarditis, obstructive hypertrophic cardiomyopathy, congenital heart disease, restrictive cardiomyopathy or constrictive pericarditis. Heart failure caused by valvular disease.
- Acute heart failure associated with uncontrolled hemodynamically relevant atrial fibrillation/flutter or ventricular rhythm disturbances.
- Acute heart failure secondary to clinical evidence of digoxin toxicity or any other drug-related toxicity.
- Significant chronic and/or acute lung disease that might interfere with the ability to interpret the dyspnea assessments or hemodynamic measurements (e.g., severe chronic obstructive pulmonary disease or acute pneumonia).
- Mechanical circulatory or ventilatory support. Prior CPAP use is allowed, if discontinued at least 2 hours prior to study drug initiation.
- Acute systemic infection/sepsis or other illness with a life expectancy less than 30 days.
- Coronary artery bypass graft, or other cardiac surgery, or major non-cardiac surgery within the last 30 days.
- Patients who received another investigational drug within 30 days prior to randomization.
- Re-randomization in the current study.
- Any factors that might interfere with the study conduct or interpretation of the results such as known drug or alcohol dependence.
- Concomitant treatment with cyclosporin A or tacrolimus.
Trial locations and contacts
35 sites in 10 countries.
35 sites in 10 countries
United States8 sites
Medical Associates, Bellebue
Bellevue, Washington
University of Alabama-Birmingham
Birmingham, Alabama
Danville Medical Center
Danville, Virginia
Denver VAMC
Denver, Colorado
Veterans Affairs Medical Center
Houston, Texas
Advanced Heart Failure and Transplant Service, Palo Alto VA Health Care System, Cardiology Section
Palo Alto, California
The Heart Hospital at Alledgheny General, Division of Cardiology
Pittsburgh, Pennsylvania
Tyler Cardiovascular Consultants
Tyler, Texas
Israel6 sites
Barzilai Hospital
Ashkelon
Carmel Medical Center
Haifa
Wolfson Medical Center
Holon
Hadassah Hospital
Jerusalem
Nazareth Hospital EMMS
Nazareth
Assaf-Harofeh Medical Center
Tsrifin
Poland5 sites
Klinika Kardiologii i Chorob Wewnetrznych, Samodzielny Publiczny Szpital
Bydgoszcz
Klinika Chorob Serca, Akademia Medyczna w Gdansku
Gdansk
I Klinika Kardiolgii, Collegium Medicum UJ
Krakow
Institute of Cardiology College, College of Medicine of Jagellonian University
Krakow
Kategra I Klinika Kardiolgii AM
Wroclaw
France4 sites
Hopital Ambroise Pare, Service de Cardiologie
Boulogne
Heart Failure clinic C.H. Dubos
Pontoise
Hopitaux Universitaires de Strasbourg, Hopital Hautepierre
Strasbourg
CHU Rangueil, Cardiologie A
Toulouse
Germany3 sites
Medizinische Klinik I, Universitatsklinikum Aachen
Aachen
Campus Virchow-Klinikum, Medizinishe Klinik mit Schwerpunkt Kardiologie
Berlin
Georg-August-Universitat Gottingen, Zentrum fur Innere Med
Göttingen
Switzerland3 sites
Centre Hospitalier Universitaire Vaudois (CHUV)
Lausanne
Cardio Centro Ticino, Servizio Cardiovasculare
Lugano
University Hospital Zurich
Zurich
United Kingdom3 sites
Glasgow Royal Infirmary
Glasgow
Hull Royal Infirmary
Hull
Scunthorpe General Hospital
Scunthorpe
Greece1 site
Dept. of Cardiology, University of Athens, Alexandra Hospital
Athens
About this study
Official title: Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group Study to Assess the Efficacy, Safety, and Tolerability of Tezosentan in Patients With Acute Heart Failure.
The randomized patients with acute heart failure will be stratified based on the presence or absence of a Swan-Ganz catheter and assigned to receive either tezosentan 5 mg/h for the first 30 minutes and 1 mg/h thereafter or matching placebo in a 1:1 manner. The duration of the treatment is 24 hours up to 72 hours. The duration of the follow-up period is 30 days after treatment initiation for death, re-hospitalizations and SAEs followed by a follow-up period of 5 months for vital status.
- Conditions
- Acute Heart Failure, Acute Decompensation of Chronic Heart Failure, New Onset of Heart Failure
- Being tested
- tezosentan
- Keywords
- acute heart failure, Actelion, tezosentan, acute decompensation of chronic heart failure, New onset of heart failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tezosentanDrug
tezosentan delivered i.v. at 20 mL/h (5 mg/h) for 30 min followed by 4ML/h (1 mg/h) for 23.5 to 71.5 h (24 to 72 h in total)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | tezosentan delivered i.v. at 20 mL/h (5 mg/h) for 30 min followed by 4ML/h (1 mg/h) for 23.5 to 71.5 h (24 to 72 h in total) Receives: Drug: tezosentan |
| 2 | Placebo comparator | Not described Receives: Drug: tezosentan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of death or worsening heart failure
Measured: 7 days following study drug initiation
Secondary outcomes (1)
effect on patient's dyspnea assessment, measured using a visual analog scale
Measured: Over first 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2007 (estimated)
- Study startApr 2003
- Primary completionJan 2005
- Study completionJan 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 735 participants (actual)
Sponsor and investigators
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00525707
- Sponsor's protocol ID
- AC-051-306
- Acronym
- VERITAS 1
- Status last verified
- Jul 2018
- First submitted
- 31 Aug 2007
- Last updated
- 10 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Cotter G, Davison BA, Milo O, Bourge RC, Cleland JG, Jondeau G, Krum H, O'Connor CM, Metra M, Parker JD, Torre-Amione G, van Veldhuisen DJ, Kobrin I, Rainisio M, Senger S, Edwards C, McMurray JJ, Teerlink JR; VERITAS Investigators. Predictors and Associations With Outcomes of Length of Hospital Stay in Patients With Acute Heart Failure: Results From VERITAS. J Card Fail. 2016 Oct;22(10):815-22. doi: 10.1016/j.cardfail.2015.12.017. Epub 2015 Dec 22.
PubMed 26721775McMurray JJ, Teerlink JR, Cotter G, Bourge RC, Cleland JG, Jondeau G, Krum H, Metra M, O'Connor CM, Parker JD, Torre-Amione G, van Veldhuisen DJ, Lewsey J, Frey A, Rainisio M, Kobrin I; VERITAS Investigators. Effects of tezosentan on symptoms and clinical outcomes in patients with acute heart failure: the VERITAS randomized controlled trials. JAMA. 2007 Nov 7;298(17):2009-19. doi: 10.1001/jama.298.17.2009.
PubMed 17986694
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group Study to Assess the Efficacy, Safety, and Tolerability of Tezosentan in Patients With Acute Heart Failure.
- ClinicalTrials.gov ID
- NCT00525707
- Acronym / sponsor ID
- VERITAS 1 / AC-051-306
- Conditions
- Acute Heart Failure, Acute Decompensation of Chronic Heart Failure, New Onset of Heart Failure
- Keywords
- acute heart failure, Actelion, tezosentan, acute decompensation of chronic heart failure, New onset of heart failure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 735 participants (actual)
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- Apr 2003
- Primary completion
- Jan 2005 (actual)
- Study completion
- Jan 2005 (actual)
- First posted
- 6 Sep 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The randomized patients with acute heart failure will be stratified based on the presence or absence of a Swan-Ganz catheter and assigned to receive either tezosentan 5 mg/h for the first 30 minutes and 1 mg/h thereafter or matching placebo in a 1:1 manner. The duration of the treatment is 24 hours up to 72 hours. The duration of the follow-up period is 30 days after treatment initiation for death, re-hospitalizations and SAEs followed by a follow-up period of 5 months for vital status.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: tezosentantezosentan delivered i.v. at 20 mL/h (5 mg/h) for 30 min followed by 4ML/h (1 mg/h) for 23.5 to 71.5 h (24 to 72 h in total) |
| 2 | Placebo comparator | Drug: tezosentan |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients 18 years of age or older.
- Male or non-breast-feeding, non-pregnant female (only females who are post menopausal, surgically sterile or practicing a reliable method of contraception).
- Acute heart failure (ischemic or non-ischemic).
- Randomization within 24 hours of hospitalization (including emergency room stay) for acute heart failure.
- Dyspnea at rest as assessed by the patient and breathing rate ³ 24/min (measured during 60 seconds).
Key exclusion criteria (21 listed)
- Baseline cardiac index > 2.5 l/min/m2 and/or PCWP < 20 mmHg within 6 hours prior to study drug initiation.
- Patients not receiving i.v. vasodilators (e.g., nitrates, nitroprusside, nesiritide) at baseline: supine systolic blood pressure < 100 mmHg. Patients receiving i.v. vasodilators (e.g., nitrates, nitroprusside, nesiritide) at baseline: supine systolic blood pressure < 120 mmHg.
- Cardiogenic shock within the last 48 hours or evidence of volume depletion.
- Ongoing myocardial ischaemia, coronary revascularisation procedure (PCI or CABG) during current admission or planned revascularisation.
- ST-segment elevation myocardial infarction or administration of thrombolytic therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tezosentantezosentan delivered i.v. at 20 mL/h (5 mg/h) for 30 min followed by 4ML/h (1 mg/h) for 23.5 to 71.5 h (24 to 72 h in total) | Drug | 1, 2 |
Primary outcome
Incidence of death or worsening heart failure
Time frame: 7 days following study drug initiation
1 secondary outcome
effect on patient's dyspnea assessment, measured using a visual analog scale
Time frame: Over first 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2018.
- Derived from this study: PubMed 26721775Cotter G, Davison BA, Milo O, Bourge RC, Cleland JG, Jondeau G, Krum H, O'Connor CM, Metra M, Parker JD, Torre-Amione G, van Veldhuisen DJ, Kobrin I, Rainisio M, Senger S, Edwards C, McMurray JJ, Teerlink JR; VERITAS Investigators. Predictors and Associations With Outcomes of Length of Hospital Stay in Patients With Acute Heart Failure: Results From VERITAS. J Card Fail. 2016 Oct;22(10):815-22. doi: 10.1016/j.cardfail.2015.12.017. Epub 2015 Dec 22.
- Derived from this study: PubMed 17986694McMurray JJ, Teerlink JR, Cotter G, Bourge RC, Cleland JG, Jondeau G, Krum H, Metra M, O'Connor CM, Parker JD, Torre-Amione G, van Veldhuisen DJ, Lewsey J, Frey A, Rainisio M, Kobrin I; VERITAS Investigators. Effects of tezosentan on symptoms and clinical outcomes in patients with acute heart failure: the VERITAS randomized controlled trials. JAMA. 2007 Nov 7;298(17):2009-19. doi: 10.1001/jama.298.17.2009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
35 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing tezosentan in people with Acute Heart Failure and Acute Decompensation of Chronic Heart Failure, run by Idorsia Pharmaceuticals Ltd. at 35 sites in 10 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 8 inclusion and 21 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 10 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, Israel, Poland, France, Germany and 5 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?
Incidence of death or worsening heart failure (time frame: 7 days following study drug initiation). 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 NCT00525707, which also lists 2 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 10 Jul 2018.