Insufficient efficacy and safety of intravenous ribavirin in treatment of haemorrhagic fever with renal syndrome caused by Puumala virus

Malinin et al., Infectious Diseases, doi:10.1080/23744235.2017.1293841, Mar 2017
Early treatmentRCT · 73 patients · Russia
Ribavirin for hantavirus
Malinin et al. Infectious Diseases · March 2017
Outcome
Improvement
Relative Risk · 95% CI
RRT
67%0.33 · 0.01–7.85
SOFA
-17%1.17 · 1.01–1.36
Time to viral clearance
-15%1.15 · 0.97–1.38
00.511.52+
← Ribavirin
reduces riskRibavirin
increases risk →
Lower progression and slower viral clearance
Not statistically significant · p = 0.49 (progression) and p = 0.11 (slower viral clearance)
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.
Important missing comments or errors? Let us know.
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).
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.
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.
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.
Abstract: es G Taylor & Francis al G ta C CrossMark Infectious Diseases ISSN: 2374-4235 (Print) 2374-4243 (Online) Journal homepage: http://www.tandfonline.com/loi/infd20 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 To link to this article: http://dx.doi.org/10.1080/23744235.2017.1293841 Published online: 03 Mar 2017. Submit your article to this journal Article views: 4 View related articles View Crossmark data 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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