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

NCT02643147 | Completed Phase 4 DMC

• 1 other identifier: 2014-001433-83
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

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

Conditions

Heart Failure

Keywords

Heart Failure; Renal Failure; Biomarker guided-therapy; Loop diuretics; Carbohydrate antigen 125

Outcome Measures

Primary Outcomes (1)

• Change in renal function (GFR)

  Glomerular filtration rate (GFR) estimated by MDRD. Prespecified interim analysis of primary outcome will be made by protocol when first 100 patients are included.

  24 and 72 hours

Secondary Outcomes (9)

• Improvement in signs and symptoms of heart failure (NYHA)

  24 and 72 hours

• Improvement in signs and symptoms of heart failure (VAS)

  24 and 72 hours

• Changes in plasma levels of natriuretic peptide (NT-proBNP)

  72 hours

• Changes in plasma levels of high sensitive troponin

  72 hours

• Time required to change intravenous diuretics to oral administration.

  Through study completion (30-day follow-up)

Study Arms (2)

CA125 guided strategy

EXPERIMENTAL

In this group loop diuretic (Furosemide) dosage will be guided by Carbohydrate Antigen 125 (CA125) plasma levels

Drug: CA125 guided strategy

Conventional strategy

ACTIVE COMPARATOR

Standard treatment strategy Therapy is based on established european guidelines

Drug: Conventional Strategy

Interventions

CA125 guided strategy DRUG

Initial dose of intravenous furosemide ≤80 mg / day regardless of prior dose of loop diuretics who were receiving.

Also known as: Loop diuretic (Furosemide) dosage in CA125 ≤35 U/ml patients

CA125 guided strategy

Conventional Strategy DRUG

The dosage of loop diuretics is done according to the presence of symptoms and signs of systemic congestion and current recommendations

Conventional strategy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with the diagnosis of acute heart failure (AHF) and the concurrence of the following conditions:
• 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).
• Elevated natriuretic peptide (NT-proBNP\> 1000 pg/ml or BNP\> 100 mg/dl).
• Creatinine ≥1,4 mg/dl on admission, provided that the estimated glomerular filtration rate less than 60 ml / min / m2.
• Intent to be treated with loop diuretics intravenously.

You may not qualify if:

• Life expectancy less than 6 months of life due to other comorbid conditions.
• Cardiogenic shock.
• Diagnosis of acute coronary syndrome in the previous 30 days.
• Restrictive or Obstructive pulmonary disease or severe degree.
• Chronic renal insufficiency in stage V (estimated glomerular filtration rate \<15 ml / min / m2) or patient previously included in known dialysis program.
• Temperature ≥38 ° C or diagnosis of pneumonia.

Sponsors & Collaborators

• Fundación para la Investigación del Hospital Clínico de Valencia: lead

Study Sites (1)

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Related Publications (1)

• de la Espriella R, Nunez E, Llacer P, Garcia-Blas S, Ventura S, Nunez JM, Sanchez R, Facila L, Vaquer JM, Bodi V, Santas E, Minana G, Mollar A, Nunez G, Chorro FJ, Gorriz JL, Sanchis J, Bayes-Genis A, Nunez J. Early urinary sodium trajectory and risk of adverse outcomes in acute heart failure and renal dysfunction. Rev Esp Cardiol (Engl Ed). 2021 Jul;74(7):616-623. doi: 10.1016/j.rec.2020.06.004. Epub 2020 Jul 2. English, Spanish.

  PMID: 32624444 DERIVED

MeSH Terms

Conditions

Heart Failure; Renal Insufficiency

Interventions

Sodium Potassium Chloride Symporter Inhibitors; Furosemide; CA-125 Antigen

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds; Mucins; Mucoproteins; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins; Antigens, Tumor-Associated, Carbohydrate; Antigens, Neoplasm; Antigens; Biological Factors; Epitopes; Biomarkers, Tumor; Biomarkers

Study Officials

• Julio Nuñez, MD, PhD

  Fundación para la Investigación del Hospital Clínico de Valencia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: December 14, 2015
• First Posted: December 31, 2015
• Study Start: January 1, 2015
• Primary Completion: January 30, 2017
• Study Completion: January 30, 2017
• Last Updated: February 13, 2018

Record last verified: 2018-02

Locations

ES (1)