2.1. Study design For the specific epidemic situation of COVID-19, we chose to conduct an open-label nonrandomized control study in the isolation ward of the national clinical research center for infectious diseases (The Third People’s Hospital of Shenzhen), Shenzhen, China. From 30 January to 14 February 2020, laboratory-confirmed patients with COVID-19 were consecutively screened, and eligible patients were included in the FPV arm of the study. Patients who had initially been treated with antiviral therapy with LPV/RTV from 24 January to 30 January 2020 were screened, and eligible patients were included in the control arm of the study. The study was conducted according to the guidelines of the Declaration of Helsinki and the principles of good clinical practice, and was approved by the ethics committee of The Third People’s Hospital of Shenzhen (No.:2020- 002-02). Written informed consent was obtained from all patients. The study was reported according to the Consolidated Standards of Reporting Trials guidelines and was registered on the Chinese Clinical Trial Registry (ID: ChiCTR2000029600)
2.3. Trial treatment FPV (Haizheng Pharmaceutical Co., 200 mg per tablet) was given orally. The dose was 1600 mg twice daily on Day 1 and 600 mg twice daily on Days 2−14. LPV/RTV (AbbVie Inc., 200 mg/50 mg per tablet) were given orally. The dose was LPV 400 mg/RTV 100 mg twice daily. Both FPV and LPV/RTV were continued until the viral clearance was confirmed or until 14 d had passed. In addition, all participants received IFN-α1b 60 µg (Beijing Tri-Prime Gene Pharmaceutical Co., 30 μg per ampule) twice daily by aerosol inhalation. Standard care included oxygen inhalation, oral or intravenous rehydration, electrolyte corre
4. Discussion This study investigated the effect of FPV versus LPV/RTV on the treatment of COVID-19. It was found that FPV was independently associated with faster viral clearance and a higher improvement rate in chest imaging. These findings suggest that FPV has significantly better treatment effects on COVID-19 in terms of disease progression and viral clearance, as compared with LPV/RTV. FPV, which is known as a prodrug, is a novel RNA-dependent RNA polymerase (RdRp) inhibitor, which has been shown to be effective in the treatment of influenza and Ebola virus [8,11–15]. Recently, a report from Wang et al. [7] showed that both FPV and remdesivir are effective in reducing the SARS-CoV-2 infection in vitro (EC50 = 61.88 μmol·L−1, CC50 > 400 μmol·L−1, SI > 6.46). The finding of the preset study confirms the hypotheses conceived from the laboratory finding: that FPV is effective treatment for COVID-19. The limitation of the present study is that it was not a randomized double-blinded placebo-controlled clinical trial, which led to inevitable selection bias in patient recruitment. However, given the high number of patients presenting simultaneously and the very high infectivity of the disease, it was ethically unacceptable to allocate patients to receive a different experimental drug using a randomization process impossible for most of the patients to understand. Furthermore, in the context of rumors and distrust of hospital isolation, using a randomized design at the outset might have led even more patients to refuse being isolated. Therefore, we chose to conduct a nonrandomized trial, in which patients consecutively admitted to the hospital during two separate periods were included in two groups, respectively. Importantly, all baseline characteristics of the two groups were comparable and the effectiveness of FPV remained significant after adjustment for potential confounders. The current study also found that early viral clearance contributed to the improvement of chest imaging on Day 14. This finding suggests that improvement of the disease may depend on inhibition of the SARS-CoV-2, and that FPV controls the disease progression of COVID-19 by inhibiting the SARS-CoV-2. Until recently, the pathogenesis of COVID-19 had not been well clarified. Since the infection of SARS-CoV-2 was thought to be self-limited and characterized by systemic inflammation reaction, symptomatic and supportive treatment was mainly recommended by the WHO and the National Health Commission of the PRC. This description is similar to MERS-CoV, for which nonspecific therapeutic interventions are often introduced to prevent severe morbidity and mortality [16]. How antivirals would contribute to control of the disease is controversial. Although there have been many registered clinical trials focusing on antiviral drugs for COVID-19, the timing, duration of treatment, and study endpoints have not been unified. In the current study, the time of viral clearance was introduced as a primary endpoint to evaluate the antiviral effect of FPV on the SARS-CoV-2 and successfully identify the priority of FPV. The relationship between the time of viral clearance and the improvement in CT image indicates that viral clearance is an ideal surrogate for the clinical endpoint. A limitation of the present study was that the relationship between the viral titer and the clinical prognosis was not well clarified. Future research could pay more attention to this point. More adverse events were observed in the control arm than in the experimental arm, and were similar to the adverse events observed in studies of AIDS treated by LPV/RTV. It is worth mentioning that the treatment duration of FPV in the present study was twice as long as that used for the treatment of influenza. However, the adverse events in the experimental arm were rare and tolerable, and none of the patients needed to discontinue FPV treatment. These results seem to suggest that the treatment duration of FPV can be prolonged if necessary. SARS-CoV-2 infection has now spread quickly all over the world. At present, no effective treatment has been demonstrated. The task at hand was to run a well-designed trial to identify effective treatments based on a high level of evidence. However, at the beginning of this study, certain conditions did not allow the randomization of patients to receive either standard care or an experimental drug. In this pilot study of a non-randomized control trial, we found that FPV showed significantly better treatment effects on COVID-19 in terms of disease progression and viral clearance; if causal, these results should be important information for establishing standard treatment guidelines to combat the SARS-CoV-2 infection. Furthermore, we introduced the time of viral clearance as a primary endpoint for experimental antiviral treatment and demonstrated it to be a surrogate of clinical endpoint
μmol·L−1, CC50 > 400 μmol·L−1, SI > 6.46). The finding of the preset study confirms the hypotheses conceived from the laboratory finding: that FPV is effective treatment for COVID-19. The limitation of the present study is that it was not a randomized double-blinded placebo-controlled clinical trial, which led to inevitable selection bias in patient recruitment. However, given the high number of patients presenting simultaneously and the very high infectivity of the disease, it was ethically unac
2.1. Study design For the specific epidemic situation of COVID-19, we chose to conduct an open-label nonrandomized control study in the isolation ward of the national clinical research center for infectious diseases (The Third People’s Hospital of Shenzhen), Shenzhen, China. From 30 January to 14 February 2020, laboratory-confirmed patients with COVID-19 were consecutively screened, and eligible patients were included in the FPV arm of the study. Patients who had initially been treated with antiviral therapy with LPV/RTV from 24 January to 30 January 2020 were screened, and eligible patients were included in the control arm of the study. The study was conducted according to the guidelines of the Declaration of Helsinki and the principles of good clinical practice, and was approved by the ethics committee of The Third People’s Hospital of Shenzhen (No.:2020- 002-02). Written informed consent was obtained from all patients. The study was reported according to the Consolidated Standards of Reporting Trials guidelines and was registered on the Chinese Clinical Trial Registry (ID: ChiCTR2000029600)
However, given the high number of patients presenting simultaneously and the very high infectivity of the disease, it was ethically unacceptable to allocate patients to receive a different experimental drug using a randomization process impossible for most of the patients to understand.
「効果」の定義があいまい (スコア:0)
アビガンじゃないけどこのレポート [nih.gov]だとコロナに効果ないって結論づけられてる。でもtable3見ると多少は効果あるように見える。
薬を飲んだら速攻治るって効果はないにしても、少しは効果あるんじゃない？
効果あるでもないでもきちんとデータを一緒に発表してもらいたい。そうしないとどう受け取ったらいいのか全く分からない。
Re: (スコア:2)
https://www.researchgate.net/publication/340000976_Experimental_Treatm... [researchgate.net]
こっちはアビガンのレポート。
偽薬を与えて実験するのが申し訳ないので、条件だけ変えて被験者全部に投薬したとか書いてある。
Re: (スコア:2)
偽薬を与えて実験するのが申し訳ないので、条件だけ変えて被験者全部に投薬したとか書いてある。
そんな事どこに書いてあるんだ？
2.1. Study design
For the specific epidemic situation of COVID-19, we chose to conduct an open-label nonrandomized control study in the
isolation ward of the national clinical research center for infectious diseases (The Third People’s Hospital of Shenzhen),
Shenzhen, China. From 30 January to 14 February 2020, laboratory-confirmed patients with COVID-19 were consecutively
screened, and eligible patients were included in the FPV arm of the study. Patients who had initially been treated with antiviral
therapy with LPV/RTV from 24 January to 30 January 2020 were screened, and eligible patients were included in the control
arm of the study. The study was conducted according to the guidelines of the Declaration of Helsinki and the principles of
good clinical practice, and was approved by the ethics committee of The Third People’s Hospital of Shenzhen (No.:2020-
002-02). Written informed consent was obtained from all patients. The study was reported according to the Consolidated
Standards of Reporting Trials guidelines and was registered on the Chinese Clinical Trial Registry (ID: ChiCTR2000029600)
2.3. Trial treatment
FPV (Haizheng Pharmaceutical Co., 200 mg per tablet) was given orally. The dose was 1600 mg twice daily on Day 1 and
600 mg twice daily on Days 2−14. LPV/RTV (AbbVie Inc., 200 mg/50 mg per tablet) were given orally. The dose was LPV
400 mg/RTV 100 mg twice daily. Both FPV and LPV/RTV were continued until the viral clearance was confirmed or until
14 d had passed. In addition, all participants received IFN-α1b 60 µg (Beijing Tri-Prime Gene Pharmaceutical Co., 30 μg per
ampule) twice daily by aerosol inhalation. Standard care included oxygen inhalation, oral or intravenous rehydration,
electrolyte corre
しきい値 1: ふつう匿名は読まない
匿名補正 -1
Re: (スコア:2)
途中で投げ出さず、４項のDiscussionまで読むことをお勧めする。「
Re: (スコア:2)
読んだよ。で、どこに「偽薬を与えて実験するのが申し訳ないので、条件だけ変えて被験者全部に投薬した」と書いてあるんだ？
4. Discussion
This study investigated the effect of FPV versus LPV/RTV on the treatment of COVID-19. It was found that FPV was
independently associated with faster viral clearance and a higher improvement rate in chest imaging. These findings suggest
that FPV has significantly better treatment effects on COVID-19 in terms of disease progression and viral clearance, as
compared with LPV/RTV. FPV, which is known as a prodrug, is a novel RNA-dependent RNA polymerase (RdRp) inhibitor,
which has been shown to be effective in the treatment of influenza and Ebola virus [8,11–15]. Recently, a report from Wang
et al. [7] showed that both FPV and remdesivir are effective in reducing the SARS-CoV-2 infection in vitro (EC50 = 61.88
μmol·L−1, CC50 > 400 μmol·L−1, SI > 6.46). The finding of the preset study confirms the hypotheses conceived from the
laboratory finding: that FPV is effective treatment for COVID-19.
The limitation of the present study is that it was not a randomized double-blinded placebo-controlled clinical trial, which
led to inevitable selection bias in patient recruitment. However, given the high number of patients presenting simultaneously
and the very high infectivity of the disease, it was ethically unacceptable to allocate patients to receive a different experimental
drug using a randomization process impossible for most of the patients to understand. Furthermore, in the context of rumors
and distrust of hospital isolation, using a randomized design at the outset might have led even more patients to refuse being
isolated. Therefore, we chose to conduct a nonrandomized trial, in which patients consecutively admitted to the hospital during
two separate periods were included in two groups, respectively. Importantly, all baseline characteristics of the two groups
were comparable and the effectiveness of FPV remained significant after adjustment for potential confounders.
The current study also found that early viral clearance contributed to the improvement of chest imaging on Day 14. This
finding suggests that improvement of the disease may depend on inhibition of the SARS-CoV-2, and that FPV controls the
disease progression of COVID-19 by inhibiting the SARS-CoV-2. Until recently, the pathogenesis of COVID-19 had not
been well clarified. Since the infection of SARS-CoV-2 was thought to be self-limited and characterized by systemic
inflammation reaction, symptomatic and supportive treatment was mainly recommended by the WHO and the National Health
Commission of the PRC. This description is similar to MERS-CoV, for which nonspecific therapeutic interventions are often
introduced to prevent severe morbidity and mortality [16]. How antivirals would contribute to control of the disease is
controversial. Although there have been many registered clinical trials focusing on antiviral drugs for COVID-19, the timing,
duration of treatment, and study endpoints have not been unified. In the current study, the time of viral clearance was
introduced as a primary endpoint to evaluate the antiviral effect of FPV on the SARS-CoV-2 and successfully identify the
priority of FPV. The relationship between the time of viral clearance and the improvement in CT image indicates that viral
clearance is an ideal surrogate for the clinical endpoint. A limitation of the present study was that the relationship between
the viral titer and the clinical prognosis was not well clarified. Future research could pay more attention to this point.
More adverse events were observed in the control arm than in the experimental arm, and were similar to the adverse events
observed in studies of AIDS treated by LPV/RTV. It is worth mentioning that the treatment duration of FPV in the present
study was twice as long as that used for the treatment of influenza. However, the adverse events in the experimental arm were
rare and tolerable, and none of the patients needed to discontinue FPV treatment. These results seem to suggest that the
treatment duration of FPV can be prolonged if necessary.
SARS-CoV-2 infection has now spread quickly all over the world. At present, no effective treatment has been
demonstrated. The task at hand was to run a well-designed trial to identify effective treatments based on a high level of
evidence. However, at the beginning of this study, certain conditions did not allow the randomization of patients to receive
either standard care or an experimental drug. In this pilot study of a non-randomized control trial, we found that FPV showed
significantly better treatment effects on COVID-19 in terms of disease progression and viral clearance; if causal, these results
should be important information for establishing standard treatment guidelines to combat the SARS-CoV-2 infection.
Furthermore, we introduced the time of viral clearance as a primary endpoint for experimental antiviral treatment and
demonstrated it to be a surrogate of clinical endpoint
しきい値 1: ふつう匿名は読まない
匿名補正 -1
Re: (スコア:2)
μmol·L−1, CC50 > 400 μmol·L−1, SI > 6.46). The finding of the preset study confirms the hypotheses conceived from the laboratory finding: that FPV is effective treatment for COVID-19.
The limitation of the present study is that it was not a randomized double-blinded placebo-controlled clinical trial, which led to inevitable selection bias in patient recruitment. However, given the high number of patients presenting simultaneously and the very high infectivity of the disease, it was ethically unac
Re:「効果」の定義があいまい (スコア:2)
そうは読めませんか？
「Study design」の所にも書いてあるけど、ランダム化せずに１月２４日から１月３０日までの患者はコントロール群に１月３０日から２月１４日までの患者をファビピラビル群に振り分けている。そこで引用してる箇所はランダム化しなかった理由を説明しているだけで、ファビピラビルをコントロール群に投薬したなどとは書かれていない。
2.1. Study design
For the specific epidemic situation of COVID-19, we chose to conduct an open-label nonrandomized control study in the
isolation ward of the national clinical research center for infectious diseases (The Third People’s Hospital of Shenzhen),
Shenzhen, China. From 30 January to 14 February 2020, laboratory-confirmed patients with COVID-19 were consecutively
screened, and eligible patients were included in the FPV arm of the study. Patients who had initially been treated with antiviral
therapy with LPV/RTV from 24 January to 30 January 2020 were screened, and eligible patients were included in the control
arm of the study. The study was conducted according to the guidelines of the Declaration of Helsinki and the principles of
good clinical practice, and was approved by the ethics committee of The Third People’s Hospital of Shenzhen (No.:2020-
002-02). Written informed consent was obtained from all patients. The study was reported according to the Consolidated
Standards of Reporting Trials guidelines and was registered on the Chinese Clinical Trial Registry (ID: ChiCTR2000029600)
しきい値 1: ふつう匿名は読まない
匿名補正 -1
Re:「効果」の定義があいまい (スコア:2)
ランダム化しなかった理由として、「患者の数が多いことや、良くわかっていない患者にファビピラビル以外を与えるのは、倫理的に許せなかった」
って、書いてるのを読んでも無視なんですね。
意訳が過ぎると指摘されるなら分かりますが、無いというのは・・・
この後に書いてある、噂とか病院への不信感を増長するのがいやだった、というのが本心だろう。という突っ込みは可能ですがね。
条件変えてというのは間違いですね。そっちは申し訳無いです。
Re:「効果」の定義があいまい (スコア:2)
偽薬を与えて実験するのが申し訳ないので、条件だけ変えて被験者全部に投薬したとか書いてある。
これの後半部分「条件だけ変えて被験者全部に投薬したとか書いてある。」というのは間違いだったが、前半部分「偽薬を与えて実験するのが申し訳ないので」という部分は「意訳」すれば書いてあるという主張？この調査ではそもそも偽薬は使われていないという点は無視するとして、著者は患者にファビピラビル以外を与えるのは「申し訳ない／倫理的に許せない」と感じているとレポート内に書いてあると？
しかし、レポートにそんな事はどこにも書かれていない。
大体、１月２４日から１月３０日までに来た患者はコントロール群に振り分けファビピラビルを使用しない治療をするという決断をしてる著者が「ファビピラビル以外を与えるのは倫理的に許せなかった」とか言い出したらかなり意味不明な自己矛盾だ。
そして「多くの患者が理解できないランダム化によって行うことが倫理的に受け入れがたい」と書いてあるのは「ファビピラビル以外を与える事」ではなく「実験薬（ファビピラビル）を与える事」。つまり真逆。
However, given the high number of patients presenting simultaneously and the very high infectivity of the disease, it was ethically unacceptable to allocate patients to receive a different experimental drug using a randomization process impossible for most of the patients to understand.
しきい値 1: ふつう匿名は読まない
匿名補正 -1