Лопинавир + Ритонавир (Lopinavir&Ritonavir)
Международное непатентованное наименование
Лопинавир + Ритонавир (Lopinavir&Ritonavir)
Торговое наименование
Калерта, Калидавир, Лопирита
Производитель, страна
AbbVie Deutschland GmbH & Co. KG, Germany; Фармасинтез, Россия; Нанофарма Девелопмент, Россия; Атолл, Россия; Lok-Beta Pharmaceuticals Pvt. Ltd., India
Механизм действия
Lopinavir and ritonavir may bind to Mpro, a key enzyme for coronavirus replication. This may suppress coronavirus activity.
Опыт использования
Approved for HIV.
Pre-clinical data show activity for other coronaviruses.
A randomized, controlled, open-label trial involving hospitalized patients with confirmed SARS-CoV-2 infection (n = 199), analyzed treatment with lopinavir; ritonavir.
- Treatment with lopinavir; ritonavir for 14 days was not associated with a difference from standard of care in the time to clinical improvement (hazard ratio 1.24; 95% CI, 0.9 to 1.72).
- Mortality at 28 days was similar between groups (19.2% vs. 25%, respectively).
- The percentages of patients with detectable viral RNA were similar. In a modified ITT analysis, lopinavir; ritonavir had a median time to clinical improvement that was shorter by 1 day (hazard ratio, 1.39%; 95% CI, 1 to 1.91).
A retrospective cohort study of hospitalized patients reviewing clinical course and risk factors for mortality included 29 patients who received lopinavir; ritonavir.
- No difference was noted in the duration of viral shedding after treatment with lopinavir; ritonavir.
Safety Concerns:
- Risk of cardiac arrhythmias (e.g., QT prolongation)
- Caution in patients with hepatic disease or hepatitis
- Significant drug interactions
Публикации COVID-19
Ivan Fan-Ngai Hung, Kwok-Cheung Lung, et al. Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. May 08, 2020. DOI: 10.1016/S0140-6736(20)31042-4.
Drs. Cao, Y. Wang, Wen, W. Liu et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. The new england journal of medicine DOI:10.1056/NEJMoa2001282.
Yueping Li1, Zhiwei Xie, et al. An exploratory randomized, controlled study on the efficacy and safety of lopinavir/ritonavir or arbidol treating adult patients hospitalized with mild/moderate COVID-19 (ELACOI). DOI:/10.1101/2020.03.19.20038984.
Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282.
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020 Mar 11. PMID: 32171076.
Yao TT, Qian JD, Zhu WY et al. A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus-A possible reference for coronavirus disease-19 treatment option. J Med Virol 2020 Feb 27. [Epub ahead of print] PMID: 32104907.
Arabi YM, Alothman A, Balkhy HH, et al. Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-beta1b (MIRACLE trial): study protocol for a randomized controlled trial. Trials. 2018 Jan 30;19(1):81.
Chu CM, Cheng VCC, Hung IFN, et al. Role of lopinavir/ritonavir in the treatment of SARS: Initial virological and clinical findings. Thorax 2004;59(3):252–256. PMID: 1498565.
Клинические исследования
1.
Название протокола
Chemoprophylaxis of SARS-CoV-2 Infection (COVID-19) in Exposed Healthcare Workers : A Randomized Double-blind Placebo-controlled Clinical Trial
Дата начала и окончания КИ
April 11, 2020 - November 30, 2020
Название организации, проводящей КИ
Centre Hospitalier Universitaire de Saint Etienne
Страны
France
Фаза
III
Кол-во пациентов
1200
2.
Название протокола
Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia
Дата начала и окончания КИ
April 11, 2016 - June 2022
Название организации, проводящей КИ
UMC Utrecht
Страны
Australia, Belgium, Canada, Croatia, Germany, Hungary, Ireland, Netherlands, New Zealand, Portugal, Romania, Spain, United Kingdom
Фаза
IV
Кол-во пациентов
6800
3.
Название протокола
An Investigation Into Beneficial Effects of Interferon Beta 1a, Compared to Interferon Beta 1b And The Base Therapeutic Regiment in Moderate to Severe COVID-19: A Randomized Clinical Trial
Дата начала и окончания КИ
April 10, 2020 - April 24, 2020
Название организации, проводящей КИ
Shahid Beheshti University of Medical Sciences
Страны
Iran
Фаза
IV
Кол-во пациентов
60
4.
Название протокола
Comparison Of Therapeutics for Hospitalized Patients Infected With SARS-CoV-2 In a Pragmatic aDaptive randoMizED Clinical Trial During the COVID-19 Pandemic (COVID MED Trial)
Дата начала и окончания КИ
April 6, 2020 - April 1, 2021
Название организации, проводящей КИ
Bassett Healthcare
Страны
USA
Фаза
II-III
Кол-во пациентов
4000
5.
Название протокола
Evaluation of Efficacy of Pharmacotherapy Treatment of COVID- 19 Infection Using Oral Levamisole and Formoterol+Budesonide Inhaler and Comparison of This Treatment Protocol With Standard National Treatment of the Disease
Дата начала и окончания КИ
April 4, 2020 - May 20, 2020
Название организации, проводящей КИ
Fasa University of Medical Sciences
Страны
Iran
Фаза
II-III
Кол-во пациентов
30
6.
Название протокола
Treatment of Moderate to Severe Coronavirus Disease (COVID-19) in Hospitalized Patients
Дата начала и окончания КИ
April 2020 - July 2021
Название организации, проводящей КИ
Nova Scotia Health Authority
Страны
Canada
Фаза
II
Кол-во пациентов
1000
7.
Название протокола
COVID-19 Ring-based Prevention Trial With Lopinavir/Ritonavir
Дата начала и окончания КИ
March 30, 2020 - March 31, 2022
Название организации, проводящей КИ
St. Michael's Hospital, Toronto
Страны
Canada
Фаза
III
Кол-во пациентов
1220
8.
Название протокола
Multi-centre, Adaptive, Randomized Trial of the Safety and Efficacy of Treatments of COVID-19 in Hospitalized Adults
Дата начала и окончания КИ
March 22, 2020 - March 2023
Название организации, проводящей КИ
Institut National de la Santé Et de la Recherche Médicale
Страны
France
Фаза
III
Кол-во пациентов
3100
9.
Название протокола
A Multi-centre, Adaptive, Randomized, Open-label, Controlled Clinical Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Patients
Дата начала и окончания КИ
March 18, 2020 - May 18, 2022
Название организации, проводящей КИ
Sunnybrook Health Sciences Centre
Страны
Canada
Фаза
II
Кол-во пациентов
440
10.
Название протокола
Multicenter Clinical Study on the Efficacy and Safety of Xiyanping Injection in the Treatment of New Coronavirus Infection Pneumonia (General and Severe)
Дата начала и окончания КИ
March 14, 2020 - April 14, 2021
Название организации, проводящей КИ
Jiangxi Qingfeng Pharmaceutical Co. Ltd.
Страны
China
Фаза
-
Кол-во пациентов
80
11.
Название протокола
Randomized Controlled Clinical Trials of Lopinavir/Ritonavir or Hydroxychloroquine in Patients With Mild Coronavirus Disease (COVID-19)
Дата начала и окончания КИ
March 11, 2020 - May 2020
Название организации, проводящей КИ
Asan Medical Center
Страны
Republic of Korea
Фаза
II
Кол-во пациентов
150
12.
Название протокола
Multi-centre, adaptive, randomized trial of the safety and efficacy of treatments of COVID-19 in hospitalized adults
Дата начала и окончания КИ
March 2020 - May 2020
Название организации, проводящей КИ
INSERM
Страны
France
Фаза
III
Кол-во пациентов
3100
13.
Название протокола
The Efficacy and Safety of Carrimycin Treatment in Patients With Novel Coronavirus Infectious Disease (COVID-19) : A Multicenter, Randomized, Open-controlled Study
Дата начала и окончания КИ
February 23, 2020 - February 28, 2021
Название организации, проводящей КИ
Beijing YouAn Hospital
Страны
China
Фаза
IV
Кол-во пациентов
520
14.
Название протокола
A Prospective, Randomized, Open, Parallel Controlled, Multicenter Clinical Study of Xiyanping Injection in Combination With Conventional Treatment for the Evaluation of the Effectiveness and Safety of Novel Coronavirus Infection Pneumonia
Дата начала и окончания КИ
February 14, 2020 - December 14, 2021
Название организации, проводящей КИ
Jiangxi Qingfeng Pharmaceutical Co. Ltd.
Страны
China
Фаза
-
Кол-во пациентов
348
15.
Название протокола
An Open-label Randomized Controlled Trial on Lopinavir/ Ritonavir, Ribavirin and Interferon Beta 1b Combination Versus Lopinavir/ Ritonavir Alone, as Treatment for 2019 Novel Coronavirus Infection
Дата начала и окончания КИ
February 10, 2020 - July 31, 2022
Название организации, проводящей КИ
The University of Hong Kong
Страны
Hong Kong
Фаза
II
Кол-во пациентов
70
16.
Название протокола
Randomized, open-label, controlled trial for evaluating of the efficacy and safety of Baloxavir Marboxil, Favipiravir, and Lopinavir-Ritonavir in the treatment of novel coronavirus pneumonia (COVID-19) patients
Дата начала и окончания КИ
February 4, 2020 - June 3, 2020
Название организации, проводящей КИ
The First Affiliated Hospital, Zhejiang University School of Medicine
Страны
China
Кол-во пациентов
30
17.
Название протокола
A randomized, open-label study to evaluate the efficacy and safety of Lopinavir-Ritonavir in patients with mild novel coronavirus pneumonia (COVID-19)
Дата начала и окончания КИ
February 3, 2020 - February 2, 2021
Название организации, проводящей КИ
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Страны
China
Кол-во пациентов
328
18.
Название протокола
An Open, Prospective/Retrospective, Randomized Controlled Cohort Study to Compare the Efficacy of Three Antiviral Drugs(Abidol Hydrochloride, Oseltamivir and Lopinavir/Ritonavir) in the Treatment of 2019-nCoV Pneumonia.
Дата начала и окончания КИ
February 1, 2020 - July 1, 2020
Название организации, проводящей КИ
Tongji Hospital
Страны
China
Фаза
IV
Кол-во пациентов
400