Terlipressin and albumin: The good, the bad, and the unattractive (with apologies to Sergio Leone)

Omar, Mahmoud; Hussaini, Trana; Yoshida, Eric M.

doi:10.3138/canlivj-2021-0010

Cited by 2 publications

(3 citation statements)

References 10 publications

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“…Similarly, an economic study under the Brazilian Public Health system found economical efficacy for terlipressin over norepinephrine. Serious adverse events have been cited to be a limiting factor for use of terlipressin (51). In the recent CONFIRM trial, gastrointestinal bleeding (4% vs 0%), sepsis (4% vs 0%), and respiratory failure (10% vs 3%) were seen in higher proportion in the terlipressin group compared with the placebo group (43).…”

Section: Main Findingsmentioning

confidence: 99%

The Comparative Effectiveness of Vasoactive Treatments for Hepatorenal Syndrome: A Systematic Review and Network Meta-Analysis*

Pitre

Kiflen

Helmeczi

et al. 2022

Critical Care Medicine

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OBJECTIVE: Hepatorenal syndrome (HRS) is associated with high rates of morbidity and mortality. Evidence examining commonly used drug treatments remains uncertain. We assessed the comparative effectiveness of inpatient treatments for HRS by performing a network meta-analysis of randomized clinical trials (RCTs). DATA SOURCES: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Medline In-Process & Other Non-Indexed Citations, Scopus, and Web of Science from inception. STUDY SELECTION AND DATA EXTRACTION: Pairs of reviewers independently identified eligible RCTs that enrolled patients with type 1 or 2 HRS. Pairs of reviewers independently extracted data. DATA SYNTHESIS: We assessed risk of bias using the Cochrane tool for RCTs and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. Our main outcomes are all-cause mortality, HRS reversal, and serious adverse events. Of 3,079 citations, we included 26 RCTs examining 1,736 patients. Based on pooled analysis, terlipressin increases HRS reversal compared with placebo (142 reversals per 1,000 [95% CI, >87.7 to >210.9]; high certainty). Norepinephrine (112.7 reversals per 1,000 [95% CI, 52.6 to >192.3]) may increase HRS reversal compared with placebo (low certainty). The effect of midodrine+octreotide (67.8 reversals per 1,000 [95% CI, <2.8 to >177.4]; very low) on HRS reversal is uncertain. Terlipressin may reduce mortality compared with placebo (93.7 fewer deaths [95% CI, 168.7 to <12.5]; low certainty). Terlipressin probably increases the risk of serious adverse events compared with placebo (20.4 more events per 1,000 [95% CI, <5.1 to >51]; moderate certainty). CONCLUSIONS: Terlipressin increases HRS reversal compared with placebo. Terlipressin may reduce mortality. Until access to terlipressin improves, initial norepinephrine administration may be more appropriate than initial trial with midodrine+octreotide. Our review has the potential to inform future guideline and practice in the treatment of HRS.

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Section: Main Findingsmentioning

confidence: 99%

The Comparative Effectiveness of Vasoactive Treatments for Hepatorenal Syndrome: A Systematic Review and Network Meta-Analysis*

Pitre

Kiflen

Helmeczi

et al. 2022

Critical Care Medicine

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“…12% exhibited adverse effects that required their removal from the study, and 4% had died during the study, mostly due to respiratory failure. 24,25 These safety issues led to the FDA's initial complete response letter stating TP could not be approved in its current form. 26 This decision was later overturned in September 2022 following further inspection.…”

mentioning

confidence: 99%

“…Several safety concerns were documented during the phase III study, including recurrence of symptoms in 17% of the patients up to 1 month following treatment with TP. 12% exhibited adverse effects that required their removal from the study, and 4% had died during the study, mostly due to respiratory failure. , These safety issues led to the FDA’s initial complete response letter stating TP could not be approved in its current form . This decision was later overturned in September 2022 following further inspection.…”

mentioning

confidence: 99%

Long-Circulating Vasoactive 1,18-Octadecanedioic Acid–Terlipressin Conjugate

Berger,

Choi,

et al. 2024

ACS Pharmacol. Transl. Sci.

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Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver disease first reported over a century ago, but its management still poses an unmet challenge. A therapeutic agent found to stabilize the condition is a short cyclic peptide, vasopressin analogue, terlipressin (TP). While TP is commonly prescribed for HRS patients in most parts of the world, it was only recently approved for use in the United States. TP exhibits short circulation half-lives and adverse side effects associated with the dose required. Herein, we present a 1,18octadecanedioic acid (ODDA) conjugate of the cyclic peptide (ODDA−TP), which enables noncovalent binding to serum albumin via native fatty acid binding modes. ODDA−TP is demonstrated to outperform TP alone in studies including in vitro cellular receptor activation, stability in plasma, pharmacokinetics, and performance in vivo in rats. Specifically, ODDA−TP had an elimination half-life 20 times that of TP alone while exhibiting a superior safety profile.

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Terlipressin and albumin: The good, the bad, and the unattractive (with apologies to Sergio Leone)

Cited by 2 publications

References 10 publications

The Comparative Effectiveness of Vasoactive Treatments for Hepatorenal Syndrome: A Systematic Review and Network Meta-Analysis*

The Comparative Effectiveness of Vasoactive Treatments for Hepatorenal Syndrome: A Systematic Review and Network Meta-Analysis*

Long-Circulating Vasoactive 1,18-Octadecanedioic Acid–Terlipressin Conjugate

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