Insufficient efficacy and safety of intravenous ribavirin in treatment of haemorrhagic fever with renal syndrome caused by Puumala virus
et al., Infectious Diseases, doi:10.1080/23744235.2017.1293841, Mar 2017
RCT 73 hospitalized patients showing no significant differences with intravenous ribavirin for treatment of haemorrhagic fever with renal syndrome (HFRS) caused by Puumala virus (PUUV). Puumala virus is relatively mild compared to other hantaviruses like Andes and there were no deaths, and only one patient in the control group required RRT.
Authors hypothesize that the lack of efficacy may be due to late initiation of therapy, the fact that PUUV disease severity is not strongly correlated with viral load (unlike Hantaan virus).
Authors do not report the baseline disease phase for patients. A secondary outcome compares patients in the oliguric phase, but authors do not report how many patients started or entered this phase.
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RRT, 67.0% lower, RR 0.33, p = 0.49, treatment 0 of 37 (0.0%), control 1 of 36 (2.8%), NNT 36, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
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SOFA, 17.1% higher, RR 1.17, p = 0.04, treatment mean 4.1 (±1.2) n=37, control mean 3.5 (±1.2) n=36.
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time to viral-, 15.5% higher, relative time 1.15, p = 0.11, treatment mean 11.2 (±4.0) n=37, control mean 9.7 (±4.0) n=36.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Malinin et al., 3 Mar 2017, Randomized Controlled Trial, Russia, peer-reviewed, 2 authors, HFRS, Puumala.
Contact: oleg.v.malinin@gmail.com.
Ribavirin is a broad-spectrum, small-molecule nucleoside analogue antiviral that inhibits hantavirus replication by depleting intracellular GTP pools via the inhibition of host inosine monophosphate dehydrogenase and by interfering directly with the viral RNA-dependent RNA polymerase.
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Insufficient efficacy and safety of intravenous ribavirin in treatment of haemorrhagic fever with renal syndrome caused by Puumala virus
Oleg V. Malinin & Alexander E. Platonov
To cite this article: Oleg V. Malinin & Alexander E. Platonov (2017): Insufficient efficacy and safety of intravenous ribavirin in treatment of haemorrhagic fever with renal syndrome caused by Puumala virus, Infectious Diseases
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INFECTIOUS DISEASES, 2017; VOL. 0, NO. 0, 1 -7
ORIGINAL ARTICLE
Insufficient efficacy and safety of intravenous ribavirin in treatment of haemorrhagic fever with renal syndrome caused by Puumala virus
Oleg V. Malinin a and Alexander E. Platonov b a Department of Infectious Diseases and Epidemiology, Izhevsk State Medical Academy, Izhevsk, Russia; b Laboratory for Zoonoses, Central Research Institute of Epidemiology, Moscow, Russia
ABSTRACT
Background: Intravenous ribavirin has been reported to be an effective treatment for haemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus in Asia. However, its therapeutic benefits for HFRS caused by Puumala virus (PUUV) in Europe are still unknown.
Methods: A randomized, open-label study of efficacy and safety of intravenous ribavirin in the treatment of HFRS was conducted in the European part of Russia. Seventy-three patients with suspected HFRS within 4 d of the onset of the disease were randomized to receive either intravenous ribavirin (33 mg/kg, followed by 16 mg/kg given every 6 h for 4 d and by 8mg/kg given every 8 h for 3 d) plus standard therapy ( n ¼ 37) or standard therapy alone ( n ¼ 36). The primary outcome was the average change from baseline in viral load over time estimated as area under the viral load curve minus baseline (AUCMB). Fifty-five patients with HFRS confirmed by nested reverse transcriptase -polymerase chain reaction (PCR) assay were included in the assessment of the efficacy. All patients entered into the clinical trial were included in the assessment of the safety.
Results: PUUV was detected in all cases of confirmed HFRS. Viral load kinetics were similar in both treatment groups. Significantly more patients receiving ribavirin than standard therapy experienced low haemoglobin level (95% vs 36%), hyperbilirubinemia (81% vs 3%), sinus bradycardia (43% vs 14%), and rash (19% vs 0%).
Conclusions: Results of the study showed insufficient efficacy and safety of intravenous ribavirin in the treatment of HFRS caused by PUUV.
KEYWORDS
Haemorrhagic fever with renal syndrome Puumala virus ribavirin
ARTICLE HISTORY
Received 1 November 2016 Revised 24 January 2017 Accepted 1 February 2017
CONTACT Oleg V. Malinin
oleg.v.malinin@gmail.com Department of Infectious Diseases and Epidemiology, Izhevsk State Medical Academy, Kommunarov Street, 281, Izhevsk 426034, Russia
http://dx.doi.org/10.1080/23744235.2017.1293841
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