COlchicine in Moderate-severe Hospitalized Patients Before ARDS to Treat COVID-19 (COMBATCOVID19)
COlchicine in Moderate-severe Hospitalized Patients Before ARDS to Treat COVID-19 (the COMBAT-COVID-19 Pilot Study)
The most prevalent complication of COVID-19 infection is respiratory failure from severe acute respiratory syndrome (SARS), the leading cause of mortality. There is increasing indication that the decompensation in severe COVD-19 infection may be due to a cytokine storm syndrome. This hyperinflammatory syndrome results in a fulminant and fatal hypercytokinemia and multiorgan failure.
Approximately 15% of patients with COVID-19 infection are hospitalized and 20-30% of these hospitalized patients require ICU care and/or mechanical ventilation. Overall mortality in hospitalized patients is approximately 20-25%. There is significant interest in therapies that can be given upstream to reduce the rate of mechanical ventilation and thus mortality.
We hypothesize that treatment with colchicine in COVID-19 moderate-severe patients may decrease the risk of progression into ARDS requiring increased oxygen requirements, mechanical ventilation, and mortality.
Tutkimuksen yleiskatsaus
Yksityiskohtainen kuvaus
Prospective, completely randomized, open labeled, controlled study. Patients will be randomized into two groups (A and B). Patients of group A will be treated under what is considered current standard of care at Maimonides Medical Center while group B patients will receive colchicine in addition to standard of care.
Treatment arm
In addition to the local standard of care for COVID 19 patients, the patient will receive colchicine PO as such:
- Loading dose of 1.2 mg followed by 0.6mg after 2 hours if without significant gastrointestinal symptoms (day 1)
- The next day 0.6mg bid for 14 days or until discharge
Patients who are on HMG-Co A Reductase Inhibitors (atorvastatin, fluvastatin, pravastatin, simvastatin), fibrates, genfibrozil, amiodarone, dronedarone or digoxin should have the colchicine dosage reduced to a loading dose of 0.6mg followed by 0.3mg after two hours (day 1) followed by 0.3mg BID for 14 days or until discharge.
If patients have significant gastrointestinal symptoms after loading, the dosage may be reduced to 0.3mg BID for the rest of the 14 day course or until discharge. If gastrointestinal symptoms continue, the medication should then be discontinued. Patients who experience sensory motor neuropathy, or symptoms and laboratory findings consistent with rhabdomyolysis should prompt immediate discontinuation of the drug. If renal function deteriorates during the treatment course and CrCl <30ml/min, colchicine should also be discontinued.
Control arm Usual medical therapy (can include medications such as hydroxychloroquine, azithromycin)
Patients should NOT receive, Remdesivir, IL-6 inhibitors (Tociluzimab, Sarilumab), JAK inhibitors, IL-1 inhibitors, or other immunomodulators for COVID-19 before randomization. Since the primary clinical endpoint is progression of disease, if the patient requires beyond 8L nasal cannula, eg. high flow O2 or mechanical ventilation, the primary clinical endpoint is met and the above experimental medications will be permitted. To rephrase, the patient will be allowed, Remdesivir, IL-6 inhibitors and other immunomodulators if then deemed medically necessary by the treating physician.
Opintotyyppi
Ilmoittautuminen (Todellinen)
Vaihe
- Vaihe 2
Yhteystiedot ja paikat
Opiskelupaikat
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New York
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Brooklyn, New York, Yhdysvallat, 11219
- Maimonides Medical Center
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
- Males and females >=18 years of age
- Willing and able to provide written informed consent prior to performing study procedures
- Currently hospitalized and requiring medical care for COVID-19
- Significant COVID-19 symptom, or judged by the treating provider to be at high risk of progression to severe COVID-19 infection
Significant COVID-19 symptoms are defined by one or more of the following:
- Dyspnea
- Respiratory frequency ≥ 30/min
- Blood oxygen saturation ≤ 93%
- AND one or more of the following: (positive PCR test or positive antibodies) or (CT/Chest X-ray consistent with COVID19 infection) or (anosmia).
Exclusion Criteria:
- Requirement of oxygen supplementation >8L nasal cannula
- Pregnancy
- Known hypersensitivity to colchicine
- Patient currently in shock or with hemodynamic instability requiring pressors
- History of cirrhosis
- Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) > 5X upper limit of normal (ULN)
- Patients with severe renal disease, CrCl <30ml/min
- Patients requiring invasive mechanical ventilation at screening or Clinical estimation that the patient will require mechanical respiratory support within 24 hours
- Patient is currently taking colchicine for other indications (gout or Familial Mediterranean Fever)
- Patient received Remdesivir, Sarilumab, Tociluzimab, Lopinavir/Ritonavir or other immunomodulator given for COVID-19 treatment (Note: Convalescent plasma infusion is not an exclusion)
- Patient is on (and cannot discontinue) a strong CYP3A4 inhibitor (eg clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, atazanavir), a moderate CYP3A4 inhbitor (eg diltiazem, verapamil, fluconazole, amprenavir, aprepitant, fosamprenavir) or a P-gp Inhibitor (eg cyclosporine, ranolazine)
- Patient is undergoing chemotherapy for cancer
- Patient is considered by the investigator, for any reason, to be unsuitable candidate for the study
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
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Active Comparator: Tavallinen hoito
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COVID Patients in this arm will receive usual care COVID19 treatment and will not receive colchine.
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Active Comparator: Colchine
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People in the colchine group will be given a starting dose of 1.2 mg followed, by 0.6mg after 2 hours if they do not have significant gastrointestinal symptoms, on day 1.
After that, they will take colchicine 0.6mg twice a day for 14 days or until discharged or release from the hospital.
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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Aikaikkuna |
|---|---|
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Percentage of Patients Requiring Supplemental Oxygen Beyond 8L Nasal Cannula
Aikaikkuna: through study completion, estimated 2 months
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through study completion, estimated 2 months
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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Aikaikkuna |
|---|---|
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Percentage of Patients Who Will Require Mechanical Ventillation
Aikaikkuna: through study completion, estimated 2 months
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through study completion, estimated 2 months
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Mortality
Aikaikkuna: through study completion, estimated 2 months
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through study completion, estimated 2 months
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Yhteistyökumppanit ja tutkijat
Sponsori
Tutkijat
- Päätutkija: Felix Yang, MD, Maimonides Medical Center
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Ensisijainen valmistuminen (Todellinen)
Opintojen valmistuminen (Todellinen)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
- Coronaviridae-infektiot
- Nidovirales-infektiot
- RNA-virusinfektiot
- Virussairaudet
- Infektiot
- Koronavirusinfektiot
- Farmakologisen vaikutuksen molekyylimekanismit
- Reumaattiset aineet
- Antineoplastiset aineet
- Tubuliinimodulaattorit
- Antimitoottiset aineet
- Mitoosin modulaattorit
- Kihtiä hillitsevät aineet
- Kolkisiini
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- 2020-04-12
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