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.
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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New York
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Brooklyn、New York、アメリカ、11219
- Maimonides Medical Center
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
- 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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
アクティブコンパレータ：いつものお手入れ
|
COVID Patients in this arm will receive usual care COVID19 treatment and will not receive colchine.
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アクティブコンパレータ：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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
|
Percentage of Patients Requiring Supplemental Oxygen Beyond 8L Nasal Cannula
時間枠：through study completion, estimated 2 months
|
through study completion, estimated 2 months
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
Percentage of Patients Who Will Require Mechanical Ventillation
時間枠：through study completion, estimated 2 months
|
through study completion, estimated 2 months
|
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Mortality
時間枠：through study completion, estimated 2 months
|
through study completion, estimated 2 months
|
協力者と研究者
捜査官
- 主任研究者：Felix Yang, MD、Maimonides Medical Center
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 2020-04-12
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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