Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial
Author(s): ,
Pere Ginès
Affiliations:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
Corresponding author. Address: Liver Unit, Hospital Clínic Barcelona, Villarroel 170, 08036 Barcelona, Spain.
,
Victor Vargas
Affiliations:
Liver Unit, Hospital Vall d’Hebron, Barcelona, Spain
,
Joan Córdoba
Affiliations:
Liver Unit, Hospital Vall d’Hebron, Barcelona, Spain
,
Xavier Xiol
Affiliations:
Grup de Recerca en malalties hepato-bilio-pancreàtiques, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
,
Miquel Navasa
Affiliations:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
,
Mónica Guevara
Affiliations:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
,
Marco Pavesi
Affiliations:
Data Management Center, EF-CLIF, Barcelona, Spain
,
Jordi Colmenero
Affiliations:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
,
Elisa Pose
Affiliations:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
,
Isabel Graupera
Affiliations:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
,
Pilar Suñé
Affiliations:
Clinical Trials Unit, Pharmacy Department, Hospital Vall d’Hebron, Barcelona, Spain
,
Xavier Ariza
Affiliations:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
,
André Nazar
Affiliations:
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
,
Marcela Manríquez
Affiliations:
Clinical Research Support Unit, Hospital Universitari de Bellvitge, L’Hospitalet de LLobregat, Barcelona, Spain
,
Meritxell Ventura
Affiliations:
Liver Unit, Hospital Vall d’Hebron, Barcelona, Spain
,
Eva Lopez Benaiges
Affiliations:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
,
Patrícia Huelin
Affiliations:
Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
,
Gloria de Prada
Affiliations:
Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
,
Núria Fabrellas
Affiliations:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
,
Francisca Márquez
Affiliations:
Liver Unit, Gastroenterology Department, Hospital Universitari de Bellvitge, Institut Català de la Salut, L'Hospitalet de Llobregat, Barcelona, Spain
,
Maria Torrens
Affiliations:
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
,
Rebeca Moreira
Affiliations:
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
,
Rita Garcia-Martínez
Affiliations:
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
,
José Castellote
Affiliations:
Grup de Recerca en malalties hepato-bilio-pancreàtiques, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
,
Marta Martín-Llahí
Affiliations:
Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
,
Macarena Simón-Talero
Affiliations:
Liver Unit, Hospital Vall d’Hebron, Barcelona, Spain
,
Cristina Solé
Affiliations:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
Elsa Solà
Affiliations:
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain
EASL LiverTree™. Ginés P. Dec 1, 2018; 256766
Pere Ginés
Pere Ginés
Contributions
Journal Abstract
References
Graphical abstract

Graphical abstract

Circulatory dysfunction is a key pathogenic factor in complications of cirrhosis. Improvement in circulatory function may prevent complications of cirrhosis. We assessed the effects of the oral vasoconstrictor midodrine associated with albumin. Midodrine plus albumin decreased renin and aldosterone levels. However, midodrine plus albumin did not prevent complications or improve survival.

Background & Aims

Patients with decompensated cirrhosis on the waiting list for liver transplantation (LT) commonly develop complications that may preclude them from reaching LT. Circulatory dysfunction leading to effective arterial hypovolemia and activation of vasoconstrictor systems is a key factor in the pathophysiology of complications of cirrhosis. The aim of this study was to investigate whether treatment with midodrine, an alpha-adrenergic vasoconstrictor, together with intravenous albumin improves circulatory dysfunction and prevents complications of cirrhosis in patients awaiting LT.

Methods

A multicenter, randomized, double-blind, placebo-controlled trial (NCT00839358) was conducted, including 196 consecutive patients with cirrhosis and ascites awaiting LT. Patients were randomly assigned to receive midodrine (15–30 mg/day) and albumin (40 g/15 days) or matching placebos for one year, until LT or drop-off from inclusion on the waiting list. The primary endpoint was incidence of any complication (renal failure, hyponatremia, infections, hepatic encephalopathy or gastrointestinal bleeding). Secondary endpoints were mortality, activity of endogenous vasoconstrictor systems and plasma cytokine levels.

Results

There were no significant differences between both groups in the probability of developing complications of cirrhosis during follow-up (p = 0.402) or one-year mortality (p = 0.527). Treatment with midodrine and albumin was associated with a slight but significant decrease in plasma renin activity and aldosterone compared to placebo (renin −4.3 vs. 0.1 ng/ml.h, p < 0.001; aldosterone −38 vs. 6 ng/dl, p = 0.02, at week 48 vs. baseline). Plasma norepinephrine only decreased slightly at week 4. Neither arterial pressure nor plasma cytokine levels changed significantly.

Conclusions

In patients with cirrhosis awaiting LT, treatment with midodrine and albumin, at the doses used in this study, slightly suppressed the activity of vasoconstrictor systems, but did not prevent complications of cirrhosis or improve survival.

Lay summary

Patients with cirrhosis who are on the liver transplant waiting list often develop complications which prevent them from receiving a transplant. Circulatory dysfunction is a key factor behind a number of complications. This study was aimed at investigating whether treating patients with midodrine (a vasoconstrictor) and albumin would improve circulatory dysfunction and prevent complications. This combined treatment, at least at the doses administered in this study, did not prevent the complications of cirrhosis or improve the survival of these patients.

Keyword(s)
Cirrhosis, Ascites, Albumin, Midodrine, Liver transplantation
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