The design of and rationale for the trial have been described previously.7 (link) The CARRESS-HF was a randomized trial that compared ultrafiltration with a strategy of diuretic-based stepped pharmacologic therapy. Patients who were hospitalized with acute decompensated heart failure as the primary diagnosis were eligible for enrollment. There was no exclusion criterion that was based on ejection fraction. All patients had worsened renal function (defined as an increase in the serum creatinine level of at least 0.3 mg per deciliter [26.5 μmol per liter]) within 12 weeks before or 10 days after the index admission for heart failure. All patients were required to have at least two of the following conditions at the time of randomization: at least 2+ peripheral edema, jugular venous pressure greater than 10 cm of water, or pulmonary edema or pleural effusion on chest radiography. Patients with a serum creatinine level of more than 3.5 mg per deciliter (309.4 μmol per liter) at the time of admission and those receiving intravenous vasodilators or inotropic agents were excluded from the study. A complete list of the trial inclusion and exclusion criteria is provided in the Supplementary Appendix , available at NEJM.org.
All study participants provided written informed consent before randomization. With the use of an automated Web-based system, patients were randomly assigned, in a 1:1 ratio, to either ultrafiltration therapy or pharmacologic therapy. A permuted-block randomization scheme was used, with stratification according to clinical site.
For patients assigned to ultrafiltration therapy, loop diuretics were to be discontinued for the duration of the ultrafiltration intervention. Fluid status was managed by means of ultrafiltration with the use of the Aquadex System 100 (CHF Solutions) according to the manufacturer’s specifications. Ultrafiltration was performed at a fluid-removal rate of 200 ml per hour. The addition of intravenous vasodilators or positive inotropic agents after randomization was prohibited unless they were deemed to be necessary as rescue therapy.
For patients assigned to stepped pharmacologic therapy, intravenous diuretics were used to manage signs and symptoms of congestion. Investigators were encouraged to decrease doses, increase doses, or continue current doses of diuretics as necessary to maintain a urine output of 3 to 5 liters per day. Recommendations regarding the use of intravenous vasodilators and inotropic agents for patients in whom the target urine output could not be attained were based on the individual patient’s blood pressure, ejection fraction, and the presence or absence of right ventricular failure at 48 hours. The details of the stepped pharmacologic-therapy algorithm are provided in theSupplementary Appendix .
In both groups, the assigned treatment strategy was to be continued until the signs and symptoms of congestion in the patient were reduced to the best extent possible. Crossover was discouraged. Diuresis or ultrafiltration could be slowed or temporarily discontinued to address technical problems or clinical care requirements, as determined by the treating physician.
All study participants provided written informed consent before randomization. With the use of an automated Web-based system, patients were randomly assigned, in a 1:1 ratio, to either ultrafiltration therapy or pharmacologic therapy. A permuted-block randomization scheme was used, with stratification according to clinical site.
For patients assigned to ultrafiltration therapy, loop diuretics were to be discontinued for the duration of the ultrafiltration intervention. Fluid status was managed by means of ultrafiltration with the use of the Aquadex System 100 (CHF Solutions) according to the manufacturer’s specifications. Ultrafiltration was performed at a fluid-removal rate of 200 ml per hour. The addition of intravenous vasodilators or positive inotropic agents after randomization was prohibited unless they were deemed to be necessary as rescue therapy.
For patients assigned to stepped pharmacologic therapy, intravenous diuretics were used to manage signs and symptoms of congestion. Investigators were encouraged to decrease doses, increase doses, or continue current doses of diuretics as necessary to maintain a urine output of 3 to 5 liters per day. Recommendations regarding the use of intravenous vasodilators and inotropic agents for patients in whom the target urine output could not be attained were based on the individual patient’s blood pressure, ejection fraction, and the presence or absence of right ventricular failure at 48 hours. The details of the stepped pharmacologic-therapy algorithm are provided in the
In both groups, the assigned treatment strategy was to be continued until the signs and symptoms of congestion in the patient were reduced to the best extent possible. Crossover was discouraged. Diuresis or ultrafiltration could be slowed or temporarily discontinued to address technical problems or clinical care requirements, as determined by the treating physician.