Treatment of type-1 hepatorenal syndrome with pentoxifylline: A randomized placebo controlled clinical trial

Jonathan Stine, Jennifer Wang, Scott L. Cornella, Brian W. Behm, Zachary Henry, Neeral L. Shah, Stephen H. Caldwell, Patrick G. Northup

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Introduction. Type-1 hepatorenal syndrome (HRS-1) portends a poor prognosis in patients with cirrhosis. Currently available medical therapies are largely ineffective, save for liver transplantation. We aimed to determine if pentoxifylline (PTX) therapy in addition to the standard of care of volume expansion with albumin and vasoconstriction with midodrine and octreotide (AMO) is safe and efficacious compared to AMO in HRS-1 treatment. Material and methods. Hospitalized subjects with decompensated cirrhosis and HRS-1 were enrolled. PTX or placebo was administered with AMO therapy for up to 14 days. The primary endpoint was HRS-1 resolution (serum creatinine ≤ 1.5 g/dL for > 24 h). Secondary endpoints were change in creatinine and MELD score, partial treatment response, 30-and 180-day overall and transplant free survival. Results. Twelve subjects with mean age 58.9 ± 6.2 years were enrolled and randomized. Mean MELD score was 26.5 ± 7.4 and 58.3% were male. Overall cohort 30- and 180-day survival was 58.3% and 33.3% respectively. Two subjects underwent liver transplantation. HRS-1 resolution (16.7% vs. 16.7%, p = 1.000), partial treatment response (33.3% vs. 16.7%, p = 0.505), change in creatinine (+0.48 g/dL, 95% CI -0.49-1.46 vs. +0.03 g/dL, 95% CI -0.64-0.70, p = 0.427), 30-day survival (66.6% vs. 50.0%, p = 0.558) and 180-day survival (50.0% vs. 16.7%, p = 0.221) were similar between the two groups. Serious adverse events necessitating treatment discontinuation were rare (n = 1, PTX). Discussion. The addition of PTX to AMO in the treatment of HRS-1 is safe when compared to the current standard of care. Future large-scale prospective study to validate the efficacy of this treatment seems warranted.

Original languageEnglish (US)
Pages (from-to)300-306
Number of pages7
JournalAnnals of Hepatology
Volume17
Issue number2
DOIs
StatePublished - Mar 1 2018

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Hepatorenal Syndrome
Pentoxifylline
Randomized Controlled Trials
Placebos
Creatinine
Survival
Therapeutics
Standard of Care
Liver Transplantation
Fibrosis
Midodrine
Octreotide
Vasoconstriction
Albumins
Prospective Studies
Transplants

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Stine, Jonathan ; Wang, Jennifer ; Cornella, Scott L. ; Behm, Brian W. ; Henry, Zachary ; Shah, Neeral L. ; Caldwell, Stephen H. ; Northup, Patrick G. / Treatment of type-1 hepatorenal syndrome with pentoxifylline : A randomized placebo controlled clinical trial. In: Annals of Hepatology. 2018 ; Vol. 17, No. 2. pp. 300-306.
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title = "Treatment of type-1 hepatorenal syndrome with pentoxifylline: A randomized placebo controlled clinical trial",
abstract = "Introduction. Type-1 hepatorenal syndrome (HRS-1) portends a poor prognosis in patients with cirrhosis. Currently available medical therapies are largely ineffective, save for liver transplantation. We aimed to determine if pentoxifylline (PTX) therapy in addition to the standard of care of volume expansion with albumin and vasoconstriction with midodrine and octreotide (AMO) is safe and efficacious compared to AMO in HRS-1 treatment. Material and methods. Hospitalized subjects with decompensated cirrhosis and HRS-1 were enrolled. PTX or placebo was administered with AMO therapy for up to 14 days. The primary endpoint was HRS-1 resolution (serum creatinine ≤ 1.5 g/dL for > 24 h). Secondary endpoints were change in creatinine and MELD score, partial treatment response, 30-and 180-day overall and transplant free survival. Results. Twelve subjects with mean age 58.9 ± 6.2 years were enrolled and randomized. Mean MELD score was 26.5 ± 7.4 and 58.3{\%} were male. Overall cohort 30- and 180-day survival was 58.3{\%} and 33.3{\%} respectively. Two subjects underwent liver transplantation. HRS-1 resolution (16.7{\%} vs. 16.7{\%}, p = 1.000), partial treatment response (33.3{\%} vs. 16.7{\%}, p = 0.505), change in creatinine (+0.48 g/dL, 95{\%} CI -0.49-1.46 vs. +0.03 g/dL, 95{\%} CI -0.64-0.70, p = 0.427), 30-day survival (66.6{\%} vs. 50.0{\%}, p = 0.558) and 180-day survival (50.0{\%} vs. 16.7{\%}, p = 0.221) were similar between the two groups. Serious adverse events necessitating treatment discontinuation were rare (n = 1, PTX). Discussion. The addition of PTX to AMO in the treatment of HRS-1 is safe when compared to the current standard of care. Future large-scale prospective study to validate the efficacy of this treatment seems warranted.",
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Stine, J, Wang, J, Cornella, SL, Behm, BW, Henry, Z, Shah, NL, Caldwell, SH & Northup, PG 2018, 'Treatment of type-1 hepatorenal syndrome with pentoxifylline: A randomized placebo controlled clinical trial', Annals of Hepatology, vol. 17, no. 2, pp. 300-306. https://doi.org/10.5604/01.3001.0010.8660

Treatment of type-1 hepatorenal syndrome with pentoxifylline : A randomized placebo controlled clinical trial. / Stine, Jonathan; Wang, Jennifer; Cornella, Scott L.; Behm, Brian W.; Henry, Zachary; Shah, Neeral L.; Caldwell, Stephen H.; Northup, Patrick G.

In: Annals of Hepatology, Vol. 17, No. 2, 01.03.2018, p. 300-306.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Treatment of type-1 hepatorenal syndrome with pentoxifylline

T2 - A randomized placebo controlled clinical trial

AU - Stine, Jonathan

AU - Wang, Jennifer

AU - Cornella, Scott L.

AU - Behm, Brian W.

AU - Henry, Zachary

AU - Shah, Neeral L.

AU - Caldwell, Stephen H.

AU - Northup, Patrick G.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Introduction. Type-1 hepatorenal syndrome (HRS-1) portends a poor prognosis in patients with cirrhosis. Currently available medical therapies are largely ineffective, save for liver transplantation. We aimed to determine if pentoxifylline (PTX) therapy in addition to the standard of care of volume expansion with albumin and vasoconstriction with midodrine and octreotide (AMO) is safe and efficacious compared to AMO in HRS-1 treatment. Material and methods. Hospitalized subjects with decompensated cirrhosis and HRS-1 were enrolled. PTX or placebo was administered with AMO therapy for up to 14 days. The primary endpoint was HRS-1 resolution (serum creatinine ≤ 1.5 g/dL for > 24 h). Secondary endpoints were change in creatinine and MELD score, partial treatment response, 30-and 180-day overall and transplant free survival. Results. Twelve subjects with mean age 58.9 ± 6.2 years were enrolled and randomized. Mean MELD score was 26.5 ± 7.4 and 58.3% were male. Overall cohort 30- and 180-day survival was 58.3% and 33.3% respectively. Two subjects underwent liver transplantation. HRS-1 resolution (16.7% vs. 16.7%, p = 1.000), partial treatment response (33.3% vs. 16.7%, p = 0.505), change in creatinine (+0.48 g/dL, 95% CI -0.49-1.46 vs. +0.03 g/dL, 95% CI -0.64-0.70, p = 0.427), 30-day survival (66.6% vs. 50.0%, p = 0.558) and 180-day survival (50.0% vs. 16.7%, p = 0.221) were similar between the two groups. Serious adverse events necessitating treatment discontinuation were rare (n = 1, PTX). Discussion. The addition of PTX to AMO in the treatment of HRS-1 is safe when compared to the current standard of care. Future large-scale prospective study to validate the efficacy of this treatment seems warranted.

AB - Introduction. Type-1 hepatorenal syndrome (HRS-1) portends a poor prognosis in patients with cirrhosis. Currently available medical therapies are largely ineffective, save for liver transplantation. We aimed to determine if pentoxifylline (PTX) therapy in addition to the standard of care of volume expansion with albumin and vasoconstriction with midodrine and octreotide (AMO) is safe and efficacious compared to AMO in HRS-1 treatment. Material and methods. Hospitalized subjects with decompensated cirrhosis and HRS-1 were enrolled. PTX or placebo was administered with AMO therapy for up to 14 days. The primary endpoint was HRS-1 resolution (serum creatinine ≤ 1.5 g/dL for > 24 h). Secondary endpoints were change in creatinine and MELD score, partial treatment response, 30-and 180-day overall and transplant free survival. Results. Twelve subjects with mean age 58.9 ± 6.2 years were enrolled and randomized. Mean MELD score was 26.5 ± 7.4 and 58.3% were male. Overall cohort 30- and 180-day survival was 58.3% and 33.3% respectively. Two subjects underwent liver transplantation. HRS-1 resolution (16.7% vs. 16.7%, p = 1.000), partial treatment response (33.3% vs. 16.7%, p = 0.505), change in creatinine (+0.48 g/dL, 95% CI -0.49-1.46 vs. +0.03 g/dL, 95% CI -0.64-0.70, p = 0.427), 30-day survival (66.6% vs. 50.0%, p = 0.558) and 180-day survival (50.0% vs. 16.7%, p = 0.221) were similar between the two groups. Serious adverse events necessitating treatment discontinuation were rare (n = 1, PTX). Discussion. The addition of PTX to AMO in the treatment of HRS-1 is safe when compared to the current standard of care. Future large-scale prospective study to validate the efficacy of this treatment seems warranted.

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