Loop Diuretic Dosage in Patients With Acute Heart Failure and Renal Failure: Conventional Versus Carbohydrate Antigen 125-guided Therapy (IMPROVE-HF)

Phase 4

Completed

• Conditions: Heart Failure
• Interventions: Drug: CA125 guided strategy; Drug: Conventional Strategy

• Registration Number: NCT02643147
• Lead Sponsor: Fundación para la Investigación del Hospital Clínico de Valencia

Brief Summary

Worsening renal function (WRF) is a frequent finding in patients with decompensated acute heart failure (AHF) and it is associated to increased length of hospitalization and higher morbidity and mortality. Traditionally, WRF in AHF setting has been attributed to low cardiac output, but recent evidence also suggests venous congestion play a crucial role. Loop diuretics are the mainstay treatment of AHF, but their use traditionally has been associated to WRF, but also renal function improvement in patients with unequivocal signs of congestion. Nevertheless, traditional symptoms or signs of patients with AHF have shown a limited accuracy to neither identify nor quantify the degree of venous congestion. Recent authors have reported that plasma levels of antigen carbohydrate 125 (CA125) are closely related to the degree of venous congestion.

The investigators hypothesize that CA125 may have a role for identifying the hyperhydrated (High CA125) patients that need high loop diuretic doses, and those with normal CA125 values needing low loop diuretic doses. In this randomized study (1:1) the investigators seek to evaluate whether a CA125 loop diuretic guided management therapy is superior to a standard strategy. The primary endpoint is the magnitude of changes of renal function at 24 and 72 hours after initiation of intravenous diuretic in an acute worsening of heart failure

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2015-12-14
• Study First Submitted QC: 2015-12-28
• Study First Posted: 2015-12-31
• Primary Completion: 2017-01-30
• Study Completion: 2017-01-30
• Status Verified: 2018-02
• Last Update Submitted: 2018-02-11
• Last Update Posted: 2018-02-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 170

Inclusion Criteria

Patients with the diagnosis of acute heart failure (AHF) and the concurrence of the following conditions:

1. Presence of symptoms (dyspnea at rest or minimal exertion) and signs attributable to congestion (signs of congestion on chest radiography, or presence of peripheral edema or ascites, or jugular venous distension at 45 degrees or presence of crackles on auscultation).
2. Elevated natriuretic peptide (NT-proBNP> 1000 pg/ml or BNP> 100 mg/dl).
3. Creatinine ≥1,4 mg/dl on admission, provided that the estimated glomerular filtration rate less than 60 ml / min / m2.
4. Intent to be treated with loop diuretics intravenously.

Exclusion Criteria

1. Life expectancy less than 6 months of life due to other comorbid conditions.
2. Cardiogenic shock.
3. Diagnosis of acute coronary syndrome in the previous 30 days.
4. Pregnancy at the time of inclusion.
5. Restrictive or Obstructive pulmonary disease or severe degree.
6. Chronic renal insufficiency in stage V (estimated glomerular filtration rate <15 ml / min / m2) or patient previously included in known dialysis program.
7. Participation in another clinical trial randomized at the time of inclusion.
8. Temperature ≥38 ° C or diagnosis of pneumonia.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CA125 guided strategy	CA125 guided strategy	In this group loop diuretic (Furosemide) dosage will be guided by Carbohydrate Antigen 125 (CA125) plasma levels
Conventional strategy	Conventional Strategy	Standard treatment strategy Therapy is based on established european guidelines

Primary Outcome Measures

Name	Time	Method
Change in renal function (GFR)	24 and 72 hours	Glomerular filtration rate (GFR) estimated by MDRD. Prespecified interim analysis of primary outcome will be made by protocol when first 100 patients are included.

Secondary Outcome Measures

Name	Time	Method
Changes in plasma levels of high sensitive troponin	72 hours
Improvement in signs and symptoms of heart failure (NYHA)	24 and 72 hours	Evaluation of dyspnea (changes in the functional class of the New York Heart Association -NYHA)
Improvement in signs and symptoms of heart failure (VAS)	24 and 72 hours	Evaluation of signs of systemic congestion, and patient global assessment (by visual analogue scale -VAS-)
Changes in plasma levels of natriuretic peptide (NT-proBNP)	72 hours
Time required to change intravenous diuretics to oral administration.	Through study completion (30-day follow-up)
Change in renal function (cystatin C)	24 h, 72 h and 30 days	Serum levels of Cystatin C
Composite of all-cause mortality plus acute heart failure related rehospitalization	30 days	Number of events in each group during 30-day follow-up
Change in renal function (urea)	24 h, 72 h and 30 days	Serum levels of urea
Change in renal function (creatinin)	24 h, 72 h and 30 days	Serum levels of creatinine

Trial Locations

Locations (1)

Hospital Clínico Universitario de Valencia; 🇪🇸 Valencia, Spain