Clinical trial NCT00524433 (phase 3, status: completed)
Conditions: acute heart failure, acute decompensation of chronic heart failure, new onset of heart failure
ICD codes: I50.811, I50.21, I50.31, I50.813, I50.23, I50.33, I50.41
Drugs: tezosentan, placebo
SMILES: COC1=CC=CC=C1OC1=C(NS(=O)(=O)C2=NC=C(C=C2)C(C)C)N=C(N=C1OCCO)C1=CC(=NC=C1)C1=NNN=N1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        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.

        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.