A Randomized, Double-Blind, Multicenter Clinical Study Comparing the Efficacy and Safety of a Drug Combination of Lopinavir/Ritonavir-Azithromycin, Lopinavir/Ritonavir-Doxycycline, and Azithromycin-Hydroxychloroquine for Patients Diagnosed with Mild to Moderate COVID-19 Infections
Purwati, Budiono, Brian Eka Rachman, Yulistiani, Andang Miatmoko, Nasronudin, Soroy Lardo, Yongki Iswandi Purnama, Mafidhatul Laely, Ike Rochmad, Taufik Ismail, Sri Wulandari, Dwi Setyawan, Alfian Nur Rosyid, Herley Windo Setiawan, Prastuti Asta Wulaningrum, Tri Pudy Asmarawati, Erika Marfiani, Shinta Karina Yuniati, Muhammad Rabiul Fuadi, Pepy Dwi Endraswari, Purwaningsih, Eryk Hendrianto, Deya Karsari, Aristika Dinaryanti, Nora Ertanti, Igo Syaiful Ihsan, Disca Sandyakala Purnama, Yuni Indrayani
Biochemistry Research International, doi:10.1155/2021/6685921
ritonavir and 500 mg of azithromycin; and Group E treated with a 400/100 mg dose of lopinavir/ritonavir and 200 mg of doxycycline. Results. 754 subjects participated in this study: 694 patients (92.4%) who presented mild symptoms and 57 patients (7.6%) classified as suffering from a moderate case of COVID-19. On the third day after treatment, 91.7%-99.2% of the subjects in Groups A-E were confirmed negative by a PCR swab test compared to 26.9% in the Control group. Observation of all groups which experienced a significant decrease in virus load between day 1 and day 7 was undertaken. Other markers, such as CRP and IL-6, were significantly lower in all treatment groups (p < 0.05 and p < 0.0001) than in the Control group. Furthermore, IL-10 and TNF-α levels were significantly elevated in all treatment groups (p < 0.0001). e administration of azithromycin to the Control group increased CRP and IL-6 levels, while reduced IL-10 and TNF-α on day 7 (p < 0.0001) compared with day 1. Decreases in ALT and AST levels were observed in all groups (p < 0.0001). ere was an increase in creatinine in the serum level of the Control, C, D, and E groups (p < 0.05), whereas the BUN level was elevated in all groups (p < 0.0001). Conclusions. e study findings suggest that the administration of lopinavir/ritonavir-doxycycline, lopinavir/ritonavir-azithromycin, and azithromycinhydroxychloroquine as a dual drug combination produced a significantly rapid PCR conversion rate to negative in three-day treatment of mild to moderate COVID-19 cases. Further studies should involve observation of older patients with severe clinical symptoms in order to collate significant amounts of demographic data.
Ethical Approval e researchers conducted the clinical trials across multicenter sites through collaboration between Universitas Airlangga, the Indonesian Intelligence Agency (BIN), and the Indonesian National Army (TNI-AD). is study was conducted in strict accordance with the approved clinical trial protocols (PPUK) provided by BPOM (No. PP.01.01.1.3.07.20.06) with an additional letter of approval from the National Institute of Health Research and Development, Indonesian Ministry of Health (Balitbangkes Kementerian Kesehatan RI), and ethical approval no. 159/KEP/2020 issued by the Ethics Committee of Universitas Airlangga Hospital (RS UNAIR) on June 23, 2020. e documents submitted to secure PPUK clearance can be found at the following URL: https://www.ina-registry.org/?act� registry_trial_detail&code_trial�11202034090121TX6YYSS.
Conflicts of Interest e authors declare no conflicts of interest regarding this work.
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{ 'indexed': { 'date-parts': [[2023, 12, 27]],
'date-time': '2023-12-27T06:02:28Z',
'timestamp': 1703656948414},
'reference-count': 35,
'publisher': 'Hindawi Limited',
'license': [ { 'start': { 'date-parts': [[2021, 2, 9]],
'date-time': '2021-02-09T00:00:00Z',
'timestamp': 1612828800000},
'content-version': 'unspecified',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by/4.0/'}],
'funder': [{'name': 'Indonesian Intelligence Agency'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'published-print': {'date-parts': [[2021, 2, 9]]},
'abstract': '<jats:p>Background. At the present time, COVID-19 vaccines are at the testing stage, and an '
'effective treatment for COVID-19 incorporating appropriate safety measures remains the most '
'significant obstacle to be overcome. A strategic countermeasure is, therefore, urgently '
'required. Aim. This study aims to evaluate the efficacy and safety of a combination of '
'lopinavir/ritonavir-azithromycin, lopinavir/ritonavir-doxycycline, and '
'azithromycin-hydroxychloroquine used to treat patients with mild to moderate COVID-19 '
'infections. Setting and Design. This study was conducted at four different clinical study '
'sites in Indonesia. The subjects gave informed consent for their participation and were '
'confirmed as being COVID-19-positive by means of an RT-PCR test. The present study '
'constituted a randomized, double-blind, and multicenter clinical study of patients diagnosed '
'with mild to moderate COVID-19 infection. Materials and Methods. Six treatment groups '
'participated in this study: a Control group administered with a 500\u2009mg dose of '
'azithromycin; Group A which received a 200/50\u2009mg dose of lopinavir/ritonavir and '
'500\u2009mg of azithromycin; Group B treated with a 200/50\u2009mg dose of '
'lopinavir/ritonavir and 200\u2009mg of doxycycline; Group C administered with 200\u2009mg of '
'hydroxychloroquine and 500\u2009mg of azithromycin; Group D which received a 400/100\u2009mg '
'dose of lopinavir/ritonavir and 500\u2009mg of azithromycin; and Group E treated with a '
'400/100\u2009mg dose of lopinavir/ritonavir and 200\u2009mg of doxycycline. Results. 754 '
'subjects participated in this study: 694 patients (92.4%) who presented mild symptoms and 57 '
'patients (7.6%) classified as suffering from a moderate case of COVID-19. On the third day '
'after treatment, 91.7%–99.2% of the subjects in Groups A–E were confirmed negative by a PCR '
'swab test compared to 26.9% in the Control group. Observation of all groups which experienced '
'a significant decrease in virus load between day 1 and day 7 was undertaken. Other markers, '
'such as CRP and IL-6, were significantly lower in all treatment groups '
'(<jats:inline-formula>\n'
' <math xmlns="http://www.w3.org/1998/Math/MathML" id="M1">\n'
' <mi>p</mi>\n'
' <mo><</mo>\n'
' <mn>0.05</mn>\n'
' </math>\n'
' </jats:inline-formula> and <jats:inline-formula>\n'
' <math xmlns="http://www.w3.org/1998/Math/MathML" id="M2">\n'
' <mi>p</mi>\n'
' <mo><</mo>\n'
' <mn>0.0001</mn>\n'
' </math>\n'
' </jats:inline-formula>) than in the Control group. Furthermore, IL-10 and '
'TNF-α levels were significantly elevated in all treatment groups (<jats:inline-formula>\n'
' <math xmlns="http://www.w3.org/1998/Math/MathML" id="M3">\n'
' <mi>p</mi>\n'
' <mo><</mo>\n'
' <mn>0.0001</mn>\n'
' </math>\n'
' </jats:inline-formula>). The administration of azithromycin to the Control '
'group increased CRP and IL-6 levels, while reduced IL-10 and TNF-α on day 7 '
'(<jats:inline-formula>\n'
' <math xmlns="http://www.w3.org/1998/Math/MathML" id="M4">\n'
' <mi>p</mi>\n'
' <mo><</mo>\n'
' <mn>0.0001</mn>\n'
' </math>\n'
' </jats:inline-formula>) compared with day 1. Decreases in ALT and AST '
'levels were observed in all groups (<jats:inline-formula>\n'
' <math xmlns="http://www.w3.org/1998/Math/MathML" id="M5">\n'
' <mi>p</mi>\n'
' <mo><</mo>\n'
' <mn>0.0001</mn>\n'
' </math>\n'
' </jats:inline-formula>). There was an increase in creatinine in the serum '
'level of the Control, C, D, and E groups (<jats:inline-formula>\n'
' <math xmlns="http://www.w3.org/1998/Math/MathML" id="M6">\n'
' <mi>p</mi>\n'
' <mo><</mo>\n'
' <mn>0.05</mn>\n'
' </math>\n'
' </jats:inline-formula>), whereas the BUN level was elevated in all groups '
'(<jats:inline-formula>\n'
' <math xmlns="http://www.w3.org/1998/Math/MathML" id="M7">\n'
' <mi>p</mi>\n'
' <mo><</mo>\n'
' <mn>0.0001</mn>\n'
' </math>\n'
' </jats:inline-formula>). Conclusions. The study findings suggest that the '
'administration of lopinavir/ritonavir-doxycycline, lopinavir/ritonavir-azithromycin, and '
'azithromycin-hydroxychloroquine as a dual drug combination produced a significantly rapid PCR '
'conversion rate to negative in three-day treatment of mild to moderate COVID-19 cases. '
'Further studies should involve observation of older patients with severe clinical symptoms in '
'order to collate significant amounts of demographic data.</jats:p>',
'DOI': '10.1155/2021/6685921',
'type': 'journal-article',
'created': {'date-parts': [[2021, 2, 10]], 'date-time': '2021-02-10T04:27:18Z', 'timestamp': 1612931238000},
'page': '1-12',
'source': 'Crossref',
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'title': 'A Randomized, Double-Blind, Multicenter Clinical Study Comparing the Efficacy and Safety of a '
'Drug Combination of Lopinavir/Ritonavir-Azithromycin, Lopinavir/Ritonavir-Doxycycline, and '
'Azithromycin-Hydroxychloroquine for Patients Diagnosed with Mild to Moderate COVID-19 Infections',
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{ 'family': 'Budiono',
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{ 'family': 'Nasronudin',
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