Coronavirus Infections, Pneumonia, Viral
Conditions
Keywords
SARS-CoV2 virus, 2019-nCOV, COVID-19, hydroxychloroquine, azithromycin
Brief summary
The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract. Around 20% of those infected have severe pneumonia and currently there is no specific or effective therapy to treat this disease. Therapeutic options using malaria drugs chloroquine and hydroxychloroquine have shown promising results in vitro and in vivo test. But those efforts have not involved large, carefully-conducted controlled studies that would provide the global medical community the proof that these drugs work on a significant scale. In this way, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in patients hospitalized with pneumonia by SARS-CoV2 virus.
Detailed description
The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract that is now spreading to several countries in the world, including Brazil. Mortality rates after infection are higher in adults over 60 and with a history of comorbidities. The most serious patients need care in intensive care units (ICU). Most of the time they depend on mechanical ventilation support due to acute respiratory distress syndrome (ARDS). Infection rates are higher than the capacity for intensive care, which represents a serious problem in medical care. Around 20% of those infected have severe pneumonia and so far it does not have a specific therapy, or even, an effective clinical management. Therapeutic options using malaria drugs chloroquine and hydroxychloroquine have shown promising results in vitro and in vivo test. A recent, small, non-randomized study with hydroxychloroquine in 36 patients infected with SARS-Cov-2 proved to be promising in the ability to reset the viral load in 6 days after starting treatment. Thus, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in the clinical evolution by the ordinal scale of 6 points in adult patients hospitalized with pneumonia caused by infection by the SARS-CoV2 virus in Brazil.
Interventions
Intervention Group: Hydroxychloroquine + azithromycin. After randomization, Hydroxychloroquine \[400mg 2x/day, 12/12h\] + azithromycin \[500mg 1x/day\]) for 10 days. Standard treatment is according to the treatment protocol for 2019-nCoV infection.
DRUGHydroxychloroquine
Active Control Group: Hydroxychloroquine. After randomization, Hydroxychloroquine \[400mg 2x/day, 12/12h\] for 10 days. Standard treatment is according to the treatment protocol for 2019-nCoV infection.
Sponsors
EMS
Hospital do Coracao
Hospital Sirio-Libanes
Brazilian Research In Intensive Care Network
Hospital Israelita Albert Einstein
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
1. Intervention Group: Hydroxychloroquine + azithromycin. After randomization, Hydroxychloroquine \[400mg 2x/day, 12/12h\] + azithromycin \[500mg 1x/day\]) for 10 days. Standard treatment is according to the treatment protocol for 2019-nCoV infection. 2. Active Control Group: Hydroxychloroquine. After randomization, Hydroxychloroquine \[400mg 2x/day, 12/12h\] for 10 days. Standard treatment is according to the treatment protocol for 2019-nCoV infection.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males and females aged \> 18 years; 2. Suspected or confirmed infection by SARS-CoV2; Presenting with one of the following: * Need for oxygen supplementation \> 4 L/min, or * Need for high-flow nasal canula, or * Need for non-invasive ventilation, or * Need for mechanical ventilation.
Exclusion criteria
1. Refusal to provide written informed consent (either the patient or a legal representative); 2. Hypersensitivity to any of the drugs used in the study (Azithromycin or Hydroxychloroquine); 3. Patients with more than 48 hours of prior study medication use; 4. Patients with onset of symptoms longer than 14 days; 5. Patients with long QT syndrome or severe ventricular arrhythmias, not protected by an implantable cardioverter defibrillators (ICD).; 6. QTc\>= 480ms; 7. Do not resuscitate order or exclusive palliative care; 8. Patients with liver disease or cirrhosis or abnormal liver enzyme tests above three times the upper limit values (alanine aminotransferase -ALT and aspartate aminotransferase - AST); 9. Patients with known retinopathy or macular degeneration; 10. Patients with history of pancreatitis; 11. Patients with concomitant use of medications that alter the absorption or excretion of azithromycin or hydroxychloroquine; 12. Breastfeeding women; 13. Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the clinical status | 15 days after randomization | Evaluation of the clinical status of patients on the 15th day after randomization defined by the Ordinal Scale of 6 points (score ranges from 1 to 6, with 6 being the worst score) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of mechanical ventilation | 29 days after randomization | Number of days that the patient was on mechanical ventilation after randomization |
| Other secondary infections | 29 days after randomization | Presence of other secondary infections |
| Time from treatment start to death | 29 days after randomization | Time from treatment start to death |
| Medium and long-term outcomes of SARS-CoV2 infection on morbimortality, daily life activities, mental health, and quality of life | 3, 6, 9 and 12 months | Morbimortality, daily life activities, mental health, and quality of life |
| Assess whether the tested therapies may be affected by leucocyte phenotype | Baseline | Leucocyte transcriptome |
| All-cause mortality | 29 days after randomization | All-cause mortality rates at 29 days after randomization |
| Evaluation of the clinical status | 7 and 29 days after randomization | Evaluation of the clinical status of patients on the 7th and 29th day after randomization defined by the Ordinal Scale of 6 points (score ranges from 1 to 6, with 6 being the worst score) |
| Number of days free from mechanical ventilation | 29 days after randomization | Number of days free from mechanical ventilation at 29 days after randomization |
| Duration of hospitalization | 29 days after randomization | Length of hospital stay on survivors |
Other
| Measure | Time frame | Description |
|---|---|---|
| Laboratory abnormalities | 29 days after randomization | Occurrence of laboratory hematimetric parameters, creatinine and bilirubin |
| Adverse events | 29 days after randomization | Occurrence of adverse events related to the use of the investigational products |
| Gastrointestinal intolerance | 29 days after randomization | Occurrence of gastrointestinal intolerance |
| QT interval prolongation | 29 days after randomization | Occurrence of QT interval prolongation |
Countries
Brazil
Outcome results
None listed