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

• Main Authors: Purwati, Purwati, BUDIONO, 079615333, BRIAN EKA RACHMAN, NIM011180226, Yulistiani, Dra., Andang Miatmoko, Andang Miatmoko, Nasronudin, Dr. dr., Sp.PD-KPTI, Soroy Lardo, Soroy Lardo, Yongki Iswandi Purnama, Yongki Iswandi Purnama, Mafidhatul Laely, Mafidhatul Laely, Ike Rochmad, Ike Rochmad, Taufik Ismail, Taufik Ismail, Sri Wulandari, Sri Wulandari, Dwi Setyawan, Dwi Setyawan, Alfian Nur Rosyid, Alfian Nur Rosyid, Herley Windo Setiawan, Herley Windo Setiawan, Prastuti Asta Wulaningrum, Prastuti Asta Wulaningrum, Tri Pudy Asmarawati, Asmarawati, ErikaMarfiani, ErikaMarfiani, ShintaKarinaYuniati, ShintaKarinaYuniati, MuhammadRabiulFuadi, MuhammadRabiulFuadi, PepyDwiEndraswari, PepyDwiEndraswari, Purwaningsih, Purwaningsih, Eryk Hendrianto, Eryk Hendrianto, Deya Karsari, Deya Karsari, Aristika Dinaryanti, Aristika Dinaryanti, Nora Ertanti, Nora Ertanti, Igo Syaiful Ihsan, Igo Syaiful Ihsan, Disca Sandyakala Purnama, Disca Sandyakala Purnama, Yuni Indrayani, Yuni Indrayani
• Format: Article PeerReviewed
• Language: English; English; English; English; English
• Published: Hindawi Publishing Corporation 2021
• Subjects: R Medicine
• Online Access: https://repository.unair.ac.id/104270/1/%28SUSULAN%29%20A%20Randomized%2C%20Double-Blind%2C%20Multicenter%20Clinical%20Study%20Comparing%20the%20Efficacy%20and%20Safety%20of%20a%20Drug%20Combination%20of%20Lopinavir_Ritonavir-Azithrom.pdf; https://repository.unair.ac.id/104270/3/A%20Randomized%2C%20Double-Blind%2C%20Multicenter%20Clinical%20Study%20Comparing%20the%20Efficacy%20and%20Safety%20of%20a%20Drug%20Combination%20of%20Lopinavir_Ritonavir-Azithromycin%2C%20Lopinavir_Ritonavir-Doxycycline%2C%20and%20Azithromycin-Hy.pdf; https://repository.unair.ac.id/104270/6/34.%20PEER_REVIEWER%20A%20Randomized%2C%20Double-Blind%2C%20Multicenter%20Clinical%20Study%20Comparing%20the%20Efficacy%20and%20Safety%20of%20a%20Drug%20Combination%20of%20Lopinavir_Rit.pdf; https://repository.unair.ac.id/104270/9/A%20Randomized%2C%20Double-Blind%2C.pdf; https://repository.unair.ac.id/104270/11/A%20Randomized%2C%20Double-Blind%2C%20Multicenter%20Clinical%20Study%20Comparing%20the%20Eff.pdf; https://repository.unair.ac.id/104270/; https://www.hindawi.com/journals/bri/2021/6685921/
• Institution: Universitas Airlangga

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. +is study aims to evaluate the efficacy and safety of a combination of lopinavir/ritonavirazithromycin, lopinavir/ritonavir-doxycycline, and azithromycin-hydroxychloroquine used to treat patients with mild to moderate COVID-19 infections. Setting and Design. +is study was conducted at four different clinical study sites in Indonesia. +e subjects gave informed consent for their participation and were confirmed as being COVID-19-positive by means of an RTPCR test. +e 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 Madministered with a 500 mg dose of azithromycin; Group A which received a 200/50 mg dose of lopinavir/ritonavir and 500 mg of azithromycin; Group B treated with a 200/50 mg dose of lopinavir/ritonavir and 200 mg of doxycycline; Group C administered with 200 mg of hydroxychloroquine and 500 mg of azithromycin; Group D which received a 400/100 mg dose of lopinavir/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 ALTand 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.