Diuretic Strategies in Acute Heart Failure and Renal Dysfunction: Conventional vs Carbohydrate Antigen 125-guided Strategy. Clinical Trial Design

Rev Esp Cardiol (Engl Ed). 2017 Dec;70(12):1067-1073. doi: 10.1016/j.rec.2017.02.028. Epub 2017 Mar 22.
[Article in English, Spanish]

Abstract

Introduction and objectives: The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1.

Methods: Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72hours, and b) renal function changes and major clinical events at 30 days.

Results: The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation.

Conclusions: We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses.

Keywords: Antígeno carbohidrato 125; Biomarker guided therapy; Carbohydrate antigen 125; Clinical outcomes; Clinical trial; Ensayo clínico; Eventos clínicos; Heart failure; Insuficiencia cardiaca; Insuficiencia renal; Renal failure; Terapia guiada por biomarcadores.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acetazolamide / therapeutic use*
  • Acute Disease
  • CA-125 Antigen / blood*
  • Cardio-Renal Syndrome / blood
  • Cardio-Renal Syndrome / complications
  • Cardio-Renal Syndrome / drug therapy*
  • Chlorthalidone / therapeutic use*
  • Creatinine / blood
  • Diuretics / therapeutic use*
  • Furosemide / therapeutic use*
  • Heart Failure / blood
  • Heart Failure / complications
  • Heart Failure / drug therapy*
  • Humans
  • Membrane Proteins / blood*
  • Patient Care Planning
  • Water-Electrolyte Imbalance / blood
  • Water-Electrolyte Imbalance / drug therapy*
  • Water-Electrolyte Imbalance / etiology

Substances

  • CA-125 Antigen
  • Diuretics
  • MUC16 protein, human
  • Membrane Proteins
  • Furosemide
  • Creatinine
  • Acetazolamide
  • Chlorthalidone