Efficacy of Sofosbuvir Plus Ledipasvir in Egyptian Patients With COVID-19 Compared to Standard Treatment
Condition: Covid19
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 3

Summary: 
      Currently there is no known effective therapy or vaccine for treatment of SARS-CoV-2,
      highlighting urgency around identifying effective therapies.

      This study aiming to evaluate the anti-HCV medications efficacy "Sofosbuvir-Ledipasvir" in
      treatment of moderate cases with SARS-COV-2 infection, in comparison to the standard
      treatment (hydroxychloroquine, oseltamivir and azithromycin).
    

Detailed description: 
      This randomized controlled clinical trial is a prospective, comparative, single blind,
      randomized study that was conducted on 250 patients, divided into two equal groups. The group
      I received Sofosbuvir plus Ledipasvir and Group II received Oseltamivir, hydroxychloroquine
      "HCQ" plus Azithromycin (the local medical committee of Almaza Fever Hospital guided standard
      treatment protocol for COVID-19).

      Randomization (in RCT only)

      Once enrolled in the study, patients randomly assigned to one of the following groups:

        -  Group I (SL group, n=125): patients received Sofosbuvir plus Ledipasvir.

        -  Group II (OCH group, n=125): patients received Oseltamivir plus HCQ & Azithromycin.

      Randomization applied through computer-generated number and concealed using sequentially
      numbered, sealed opaque envelope.

      Group I Patients assigned to this group (125 patients) were received Sofosbuvir plus
      Ledipasvir (FDA approved Anti-HCV drug since 2014, with Reference ID: 4081324), once daily
      for 15 to 21days as minimum and maximum duration of therapy, respectively.

      Additional conservative medications were given including, third generation cephalosporines
      (Ceftriaxone 2 gm /24 hours) for 7 days, methylprednisolone 1 mg/kg/day for 7 days; and
      prophylactic low molecular weight heparin (enoxaparine) 40 mg/24 hours was given throughout
      hospitalization period.

      Patients were evaluated as scheduled on day 0,5,10 & 15 (also, day 21 if extended duration)
      clinically, laboratory investigations including RT-PCR & C.T chest. RT-PCR with negative
      result was repeated after 24-48 hrs.

      Medications stopped any time if there was any clinical, radiological or laboratory
      deterioration.

      Group II

      Patients in this group (125 patients) were received the local medical committee of Almaza
      Fever Hospital guided standard treatment protocol for COVID-19:

        -  Oseltamivir 150 mg q 12 hours for 10 days ;

        -  HCQ 400 q 12 hours for one day followed by 200mg q 12 hours for 9 days ; and

        -  Azithromycin 500mg once daily for 1 day , followed by 250mg once daily for 6 days.

        -  Additional conservative medications were also given. Patients were evaluated as
           scheduled on day 0, 5 & 11 clinically, laboratory Investigations including RT-PCR & C.T
           chest. RT-PCR with negative result was repeated after 24-48 hrs. Medication were stopped
           any time, if there was any clinical, radiological or laboratory deterioration.

      2.3 Assessment tools

      Basic investigations were applied for all patients on day 0 , repeated on days 5 ,10 & 15 or
      earlier regarding physician order , including :

        -  CBC, NLR "neutrophil lymphocyte ratio ".

        -  ESR.

        -  AST, ALT, creatinine; fasting blood glucose.

        -  ECG.

        -  C.T chest , pneumonia was assessed on admission using CT Severity Scoring System
           (CT-SSS) and CO-RADS ( Percentage per lobe with max of 5 points for each lobe and 25
           points for both lungs ; Right Lung" RUL , RML & RLL " ; Left lung " LUL & LLL " ) (11)

      Follow up CT chest was repeated on day 5, 10 and day15 or earlier according to physician's
      request. It was reported as progressive, regressive, stationary or resolved (progressive:
      crazy paving +↑CTSS ± consolidation; regressive: i.e. absorption (resolved crazy paving
      pattern +↓CTSS (12); Cured: complete resolution of pneumonic patches).

      Other investigations were asked and repeated when needed including:

        -  LDH.

        -  TG.

        -  D. dimmer.

        -  S.Ferritin.

        -  Interleukin 6 level.

        -  Abdominal U.S.

      COVID-19 RT-PCR test was done by extraction of the DNA of the virus by using either device
      (QIA cube or QIA symphony), it takes 70 minutes for every 12 sample on QIA cube or 5 hours
      for every 96 samples on the QIA symphony. Then the process was applied for the preparation
      and implementation of the RT-PCR step by using chemicals for detection of the COVID-19, which
      takes from one and half hour to two hours for 72 samples.

      Discharge criteria

        -  Resolution of symptoms (Normal body temperature for at least 3 days and significantly
           improved respiratory symptoms).

        -  Radiological improvement of pneumonic pattern in CT chest.

        -  Documented virological clearance in 2 samples at least 24 hours apart.

        -  There was no co-morbidities or complications, which require hospitalization.

        -  SpO2 > 93 % without assisted oxygen inhalation.

        -  Discharge approved by multi-disciplinary medical team.
    

Intervention name(s): Sofosbuvir plus Ledipasvir
Intervention type(s): Drug
Intervention description(s): Sofosbuvir plus Ledipasvir, once daily for 15 to 21days
Oseltamivir 150 mg q 12 hours for 10 days ;
HCQ 400 q 12 hours for one day followed by 200mg q 12 hours for 9 days ; and
Azithromycin 500mg once daily for 1 day , followed by 250mg once daily for 6 days.
Other intervention name(s): Oseltamivir plus Hydroxychloroquine & Azithromycin
Intervention MeSH terms: Azithromycin; Hydroxychloroquine; Sofosbuvir; Oseltamivir; Ledipasvir
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This randomized controlled clinical trial is a prospective, comparative, single blind, randomized study that was conducted on 250 patients, divided into two equal groups. The group I received Sofosbuvir plus Ledipasvir and Group II received Oseltamivir, hydroxychloroquine "HCQ" plus Azithromycin (the local medical committee of Almaza Fever Hospital guided standard treatment protocol for COVID-19)
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: SARS-COV-2; Covid-19; Sofosbuvir- Ledipasvir; Hydroxychloroquine