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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00524433




Registration number
NCT00524433
Ethics application status
Date submitted
31/08/2007
Date registered
3/09/2007
Date last updated
10/07/2018

Titles & IDs
Public title
Tezosentan in the Treatment of Acute Heart Failure
Scientific 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.
Secondary ID [1] 0 0
AC-051-307
Universal Trial Number (UTN)
Trial acronym
VERITAS 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Heart Failure 0 0
Acute Decompensation of Chronic Heart Failure 0 0
New Onset of Heart Failure 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - tezosentan
Treatment: Drugs - placebo

Experimental: 1 - tezosentan

Placebo Comparator: 2 -


Treatment: Drugs: tezosentan
tezosentan delivered i.v. at 20 mL/h (5 mg/h) for 30 min followed by 4 mL/h (1 mg/h) for 23.5 to 71.5 h (24 to 72 h in total)

Treatment: Drugs: placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of death or worsening heart failure
Timepoint [1] 0 0
within 7 days following study drug initiation
Secondary outcome [1] 0 0
Patient's dyspnea assessment, measured using a visual analog scale
Timepoint [1] 0 0
Over first 24 hours

Eligibility
Key inclusion criteria
- 1.Patients 18 years of age or older. 2.Male or non-breast-feeding, non-pregnant female
(only females who are post menopausal, surgically sterile or practicing a reliable
method of contraception).

3.Acute heart failure (ischemic or non-ischemic). 4.Randomization within 24 hours of
hospitalization (including emergency room stay) for acute heart failure.

5.Dyspnea at rest as assessed by the patient and breathing rate ³ 24/min (measured
during 60 seconds).

6.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).

7.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).

8.Written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Criteria only for patients hemodynamically monitored:

1. 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:

2. 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.

3. Cardiogenic shock within the last 48 hours or evidence of volume depletion.

4. Ongoing myocardial ischaemia, coronary revascularisation procedure (PCI or CABG)
during current admission or planned revascularisation.

5. ST-segment elevation myocardial infarction or administration of thrombolytic
therapy.

6. Baseline creatinine = 2.5 mg/dl (221 mmol/l).

7. Baseline hemoglobin < 10 g/dl or a hematocrit < 30%.

8. Hemodialysis, ultrafiltration or peritoneal dialysis within the last 7 days.

9. Heart failure due to active myocarditis, obstructive hypertrophic cardiomyopathy,
congenital heart disease, restrictive cardiomyopathy or constrictive
pericarditis. Heart failure caused by valvular disease.

10. Acute heart failure associated with uncontrolled hemodynamically relevant atrial
fibrillation/flutter or ventricular rhythm disturbances.

11. Acute heart failure secondary to clinical evidence of digoxin toxicity or any
other drug-related toxicity.

12. 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).

13. Mechanical circulatory or ventilatory support. Prior CPAP use is allowed, if
discontinued at least 2 hours prior to study drug initiation.

14. Acute systemic infection/sepsis or other illness with a life expectancy less than
30 days.

15. Coronary artery bypass graft, or other cardiac surgery, or major non-cardiac
surgery within the last 30 days.

16. Patients who received another investigational drug within 30 days prior to
randomization.

17. Re-randomization in the current study.

18. Any factors that might interfere with the study conduct or interpretation of the
results such as known drug or alcohol dependence.

19. Concomitant treatment with cyclosporin A or tacrolimus.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2005
Sample size
Target
Accrual to date
Final
713
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Alfred Hospital, Monash University, Central and Eastern School - Prahran
Recruitment hospital [2] 0 0
Concord Repatriation Hospital - Concord NSW
Recruitment hospital [3] 0 0
Queen Elizabeth Hospital - Woodville SA
Recruitment postcode(s) [1] 0 0
- Prahran
Recruitment postcode(s) [2] 0 0
- Concord NSW
Recruitment postcode(s) [3] 0 0
- Woodville SA
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
Czechia
State/province [11] 0 0
Brno
Country [12] 0 0
Czechia
State/province [12] 0 0
Liberec
Country [13] 0 0
Czechia
State/province [13] 0 0
Prague
Country [14] 0 0
Czechia
State/province [14] 0 0
Usti nad Labem
Country [15] 0 0
Germany
State/province [15] 0 0
Berlin
Country [16] 0 0
Germany
State/province [16] 0 0
Greifswald
Country [17] 0 0
Germany
State/province [17] 0 0
Langen
Country [18] 0 0
Germany
State/province [18] 0 0
Lubeck
Country [19] 0 0
Germany
State/province [19] 0 0
Regensburg
Country [20] 0 0
Hungary
State/province [20] 0 0
Budapest
Country [21] 0 0
Hungary
State/province [21] 0 0
Debrecen
Country [22] 0 0
Hungary
State/province [22] 0 0
Szeged
Country [23] 0 0
Italy
State/province [23] 0 0
Brescia
Country [24] 0 0
Italy
State/province [24] 0 0
Rozzano (MI)
Country [25] 0 0
Norway
State/province [25] 0 0
Alesund
Country [26] 0 0
Norway
State/province [26] 0 0
Oslo
Country [27] 0 0
Norway
State/province [27] 0 0
Stavanger
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Birmingham
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Bridlington
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Glasgow
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Leicester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Idorsia Pharmaceuticals Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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. 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00524433
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00524433