Table 1.
Prior decongestion strategy trials in ADHF
| Trial | n | Decongestion strategy | Diuretic monitoring and titration strategy | Primary outcome | Limitations to generalization | Main result(s) |
|---|---|---|---|---|---|---|
| EVEREST [15] | 4133 |
1) Tolvaptan + usual care 3) Placebo + usual care |
No standardized diuretic strategy | 7-day composite: change in GCS and body weight |
1) Excluded those with LVEF > 40% 2) Excluded those with SCr > 3.5 mg/dL 3) Enrolled up to 48 h after hospitalization |
Greater improvement in 7-day composite outcome with tolvaptan compared to placebo |
| DOSE [16] | 308 |
1) High-dose diuretic strategy 2) Low-dose diuretic strategy (stratified by bolus vs. continuous infusion) |
Standardized initial diuretic dose based on oral dose No standardized strategy to guide dosing change at 48 h or additional open-label diuretic doses |
Co-primary at 72 h 1) Patient symptom assessment 2) Change in SCr from 3) baseline |
1) Excluded those with SCr > 3.0 mg/d 2) L 3) Physician discretion at 48 h for dosing change or change to open-label 4) Intervention stopped at 72 h |
No significant difference in bolus vs. continuous infusion or high-dose vs. low-dose for patient-reported symptoms or change in creatinine at 72 h |
| CARRESS [17] | 188 |
1) Stepped pharmacologic 2) therapy 3) Ultrafiltration |
Standardized diuretic titration based on urine output volume |
Bivariate change in 2 outcomes at 96 h: 1) Creatinine 2) Body weight |
1) Only enrolled those with WRF but excluded those with SCr > 3.5 mg/dL 2) Open-label design 3) Intervention stopped at 96 h |
Ultrafiltration inferior to stepped pharmacologic therapy at 96 h for creatinine and body weight |
| ROSE-AHF [18] | 360 |
1) Low-dose dopamine 2) Low-dose nesiritide 3) Usual care |
Standardized initial diuretic dose based on oral dose No standardized strategy to guide diuretic dosing change starting at 24 h |
Co-primary at 72 h: changes in urine volume and cystatin-C |
1) Excluded patients with eGFR > 60 or < 15 mL/min/m2 and anticipated hospital stay > 72 h 2) Intervention stopped at 72 h |
No difference at 72 h from usual care for either dopamine or nesiritide group on change in urine volume or cystatin |
| 3T Trial [19] | 60 |
Standardized loop diuretics plus either: 1) Oral metolazone 2) IV chlorothiazide 3) Tolvaptan |
Standardized diuretic titration based on urine output volume | Weight loss at 48 h |
1) Only enrolled patients with diuretic resistance 2) Intervention stopped at 48 h 3) Excluded patients with eGFR < 15 mL/min/m2 |
Similar weight loss in all three groups without a statistically detectable between group difference |
| ADVOR [20] | 519 |
Standardized loop diuretics plus either: 1) Acetazolamide 2) Placebo |
Standardized diuretic titration based on urine output volume | Achievement of decongestion at 72 h by blinded investigator clinical assessment |
1) Excluded patients requiring IV furosemide doses > 80 mg prior to enrollment 2) Excluded patients on SGLT2i 3) Intervention stopped at 72 h 4) Excluded patients with eGFR < 20 mL/min/m2 |
Significantly greater successful decongestion in acetazolamide group compared to placebo No difference in all-cause mortality or HF hospitalization at 3 months between groups |
| CLOROTIC [21] | 230 |
Standardized loop diuretics plus either: 1) Hydrochlorothiazide 2) Placebo |
Standardized initial diuretic dose based on oral dose No standardized strategy to guide diuretic dosing change starting at 24 h |
Co-primary endpoints: 1) Change in body weight at 72 h compared to baseline 2) Patient-reported dyspnea at 72 h compared to baseline |
1) Lower than anticipated enrollment 2) Unbalanced baseline characteristics between groups 3) Did not specify degree of congestion/volume overload needed for inclusion 4) Long-term renal function not monitored 5) Intervention stopped at 5 days |
Statistically greater weight loss, but no difference in patient-reported dyspnea at 72 h in HCTZ group compared to placebo No difference in mortality or hospitalization |
GCS global clinical status, WRF worsening renal function, LVEF left ventricular ejection fraction, IV intravenous, SCr serum creatinine, eGFR estimated glomerular filtration rate, SGLT2i sodium-glucose co-transporter 2 inhibitors