Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04472611 |
| Other study ID # |
2000027950 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
October 30, 2020 |
| Est. completion date |
March 30, 2022 |
Study information
| Verified date |
April 2023 |
| Source |
Yale University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This is a pragmatic randomized open-label study of the safety and efficacy of the combination
of colchicine and Rosuvastatin in addition to standard of care (SOC) compared to SOC alone in
hospitalized patients with SARS-CoV-2
Description:
This is a prospective 1:1 randomized open-label clinical trial to investigate the safety and
efficacy of the combination of Colchicine + Rosuvastatin added to standard of care (SOC)
compared to SOC alone in hospitalized subjects with moderate COVID-19.
Subjects will be screened during admission to hospital. Patients with confirmed SARS-CoV-2
infection, and meeting all other inclusion and exclusion criteria, will be randomized to
either Colchicine+Rosuvastatin treatment or SOC for the duration of hospitalization. SOC will
be guided by the YNHH SARS-CoV-2 Therapeutics Group. In cases where patients require
randomization in another trial evaluating an experimental drug, they will continue on study
drug. Patients will be assessed daily while hospitalized for clinical, biomarker, safety, and
laboratory parameters based on SOC.
Colchicine is an extensively studied oral anti-inflammatory agent with a well-defined safety
profile. Colchicine, by inhibiting tubulin polymerization and clathrin-mediated endocytosis
has the potential to inhibit SARS-CoV-2 cell entry. In addition, colchicine has a direct
anti-inflammatory effect by inhibiting the NLRP3 inflammasome activation which in turn has
the potential to reduce the SARS-CoV-2-induced cytokine storm. Statins also have direct
anti-inflammatory effects by reducing chemokine release, adhesion molecules, and modulating T
cell activity and have the potential to prevent SARS-CoV-2 related endothelial dysfunction
and may reduce the morbidity and mortality associated with COVID-19. Rosuvastatin, in
particular, appears to have direct antiviral properties by binding and inhibiting the active
site of the main protease enzyme (Mpro) of SARS-CoV-2.1
The combination Colchicine + Rosuvastatin may have a synergetic effect to antagonize
SARS-CoV-2 infection, modulate the inflammatory response and to reduce morbidity and
mortality associated with acute respiratory distress syndrome (ARDS) and myocardial injury in
COVID-19 patients.
Both drugs have been in use for decades for gout and pericarditis (colchicine) and
hyperlipidemia, coronary disease (CAD) and diabetes (rosuvastatin/Crestor), and have been
tested in thousands of patients used individually and in combination with a low and well
characterized risk profile. Colchicine and rosuvastatin are currently used as standard of
care in COVID-19 patients whether due to pre-existing CAD, gout or pericarditis or acute
presentations with acute coronary syndromes or acute gout with no expected added risk in the
population being studied.
This study is not intended to support a labeling change or advertising claim for either drug,
and the study will be conducted in compliance with the requirements of Yale University's IRB
review and a research IND.
Subjects will be screened within 48 hours of hospital admission. Patients with real-time
reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infection and
meeting all inclusion and exclusion criteria, will be randomized to either Colchicine +
Rosuvastatin treatment in addition to SOC or SOC alone for the duration of hospitalization.
Subjects will be randomized in a 1:1 manner to one of two arms:
Active treatment:
In addition to SOC* subjects randomized to active treatment will receive:
- Rosuvastatin: 40mg daily AND
- Colchicine: 0.6mg twice daily for 3 days then 0.6mg daily Note: Dose adjustment based on
medical conditions and drug interactions (see section §7.4.1). Subjects previously on
chronic statin therapy will be eligible for enrollment in the trial, and if randomized
to active treatment, chronic statin therapy will be discontinued and replaced by
rosuvastatin 40 mg for 30 days or hospital discharge and resumed thereafter.
Standard of Care Controls:
Subjects will undergo SOC treatment determined by the primary care team and the YNHH
treatment algorithm for hospitalized patients with COVID-19.
*All standard of care treatments for hospitalized subjects with SARS-CoV-2 are permitted
concurrently with the study intervention. This only includes treatments approved by the Yale
SOC treatment Committee. Concomitant therapy will be performed according to standard
practice, local standards of care and published guidelines. Subjects will not be permitted to
participate in other investigational studies. Methods for identifying drug interactions and
dose adjustment are listed in section §7.4.1 of the protocol. Drug discontinuation is only
permitted with documented adverse reactions (section §7.4.3).
Treatment will continue for a total of 30 days. If the subject is discharged the treatment
will stop at that time.
