Patients hospitalised with heart failure, volume overload and renal impairment, who require loop diuretic therapy and hemodynamic monitoring for clinical reasons MedDRA version: 9.1 Level: LLT Classification code 10000803 Term: Acute heart failure
Conditions
Interventions
Product Name: Rolofylline Injectable Emulsion
Product Code: MK-7418/KW-3902
Pharmaceutical Form: Emulsion for injection
CAS Number: 136199-02-5
Current Sponsor code: MK-7418/KW-3902
Other descriptive
Sponsors
NovaCardia, Inc. (A wholly owned subsidiary of Merck & Co., Inc.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to provide written informed consent 2. Male or female 18 years of age or greater 3. Current use of oral furosemide =80 mg/day or IV furosemide =40 mg/day (or equivalent dose of oral/IV loop diuretic) 4. Stable heart failure therapy (excluding diuretics) for =24 hours prior to screening (treatment with ACE inhibitors, ARBS, digoxin, aldosterone blockers, nitrates, hydralazine, and other diuretics are allowed as long as doses are stable for at least 24 hours prior to screening) 5. Impaired renal function defined as a creatinine clearance between 20-80 mL/min using the Cockcroft-Gault equation (corrected for height in edematous or obese patients =100 kg) based on serum creatinine measurements done within 24 hours of screening (13) 6. BNP >500 pg/mL OR NT-pro-BNP >2000 pg/mL within 24 hours of screening 7. Systolic blood pressure =95 mmHg (patients with a systolic blood pressure of 90 – 94 mmHg at randomization may be included if their usual systolic blood pressure measurements are consistently within this range while clinically stable) 8. Patients require at least 12 hours of hemodynamic monitoring in the period after screening. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 9. Pregnant or breast feeding women. Women of child bearing potential must have a negative urine or serum pregnancy test prior to enrollment. NOTE: Appropriate contraception (hormonal contraceptives [such as birth control pills, Depo-Provera, or contraceptive implants], condoms, diaphragms, spermicidal foam or jelly, surgical sterilization [hysterectomy or tubal ligation] or intrauterine device) should be used through Day 14. 10. Acute contrast induced nephropathy 11. Temperature >38°C (100.4 °F; oral or adjusted axillary/rectal temperature) or sepsis or active infection requiring IV anti-microbial treatment 12. Administration of oral or IV loop diuretic within 3 hours prior to the initial screening 13. Serum potassium 120 beats per minute) 23. Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy. This criterion does not include restrictive patterns seen on Doppler. 24. Known hepatic impairment with a total bilirubin >3 mg/dL, or an albumin 35 kg/m2 26. Hgb <8 g/dL or Hct <25% or the need for a blood transfusion 27. Non-cardiac pulmonary edema, including suspected sepsis 28. Administration of an investigational drug or device, or participation in another trial, within 30 days before randomization 29. Current or anticipated therapy with atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, or voriconazole 30. Systolic blood pressure =160 mmHg at randomization 31. Inability to follow instructions or comply with follow-up procedures 32. Allergy to soybean oil, eggs, or benzodiazepines 33. History of seizure (except febrile seizure) 34. Stroke within 2 years 35. History of or current brain tumor of any etiology 36. Brain surgery within 2 years 37. Encephalitis/meningitis within 2 years 38. History of penetrating head trauma 39. Closed head injury with loss of consciousness (LOC) over 30 minutes within 2 years 40. History of drug or alcohol abuse or at risk for alcohol withdrawal seizures 41. Advanced
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objectives of this study are to estimate the effects of rolofylline, alone in addition to loop diuretic therapy, on pulmonary capillary wedge pressure, as well as other hemodynamic parameters, and to estimate the effects of rolofylline on diuresis and natriuresis in patients with heart failure and renal impairment.;Secondary Objective: All adverse events will be monitored and reported during the study treatment period to determine safety. Adverse events (AEs) will be recorded after obtaining informed consent through Day 7. Serious Adverse Events (SAEs) will be recorded through Day 14. Physical examination, hemodynamic, and laboratory data will also be evaluated. ;Primary end point(s): Change in PCWP 4 and 8 hours after initiation of study drug. | — |
Countries
Czech Republic, Germany, Italy
Outcome results
None listed