Treatment With Human Umbilical Cord-derived Mesenchymal Stem Cells for Severe Corona Virus Disease 2019 (COVID-19)
A Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Human Umbilical Cord-derived Mesenchymal Stem Cells in the Treatment of Severe COVID-19 Patients
調査の概要
状態
詳細な説明
The Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection has unprecedentedly spread in the worldwide and been declared as a pandemic by the world health organization. COVID-19 is characterized by sustained cytokines production and hyper-inflammation, can cause clusters of severe respiratory illness with a fatality rate around 2-5%. There are currently no prophylactic vaccine and no specific antiviral treatment agents available recommended for COVID-19. Therefore, it is urgent to find a safe and effective therapeutic approach to COVID-19.
During the last decade, the promising features of mesenchymal stem cells (MSCs), including their regenerative properties and ability to differentiate into diverse cell lineages, have generated great interest among researchers whose work has offered intriguing perspectives on cell-based therapies for various diseases. These findings seem to highlight that the beneficial effect of MSC-based treatment could be principally due by the immunomodulation and regenerative potential of these cells. MSCs could significantly reduce the pathological changes of lung and inhibit the cell-mediated immune inflammatory response induced by influenza virus in animal model . MSCs has been shown to reduce nonproductive inflammation and affect tissue regeneration and is being evaluated in patients with ARDS. Our phase I preliminary data of parallel assignment study(NCT04252118) showed that three doses of MSCs was safe in patients with COVID-19. Randomized control trial is needed to assess efficacy and safety.
The investigators will do a prospective, double-blind, multicentre, randomised trial to assess treatment with three intravenous doses of MSCs compared with placebo. 90 severe COVID-19 patients will be recruited in China. 60 patients will receive i.v. transfusion 3 times of MSCs (4.0*10E7 cells per time) and the standard of care as the treated group. In addition, the 30 patients will receive placebo and standard of care as control group.
Change in lesion proportion (%) of full lung volume from baseline to day 10, day28 and 90, change in consolidation/ ground-glass lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90, time to clinical improvement in 28 days, mMRC (Modified Medical Research Council) dyspnea scale, 6-minute walk test, maximum vital capacity (VCmax), Diffusing Capacity (DLCO), oxygen saturation, oxygenation index, duration of oxygen therapy, side effects, immunological characteristics (immune cells, inflammatory factors, etc.) will be evaluated during the 90 days follow up.
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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Hubei
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Wuhan、Hubei、中国、430000
- General Hospital of Central Theater Command
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Wuhan、Hubei、中国、430000
- Maternal and Child Hospital of Hubei Province
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Wuhan、Hubei、中国、430000
- Wuhan Huoshenshan Hospital
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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
Inclusion Criteria:
- Male or female, aged at 18 years (including) -75 years old
- Hospitalized
- Laboratory confirmation of SARS-CoV-2 infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source
- Pneumonia that is judged by computed tomography
- In accordance with any one of the following : 1)dyspnea (RR ≥ 30 times / min), 2)finger oxygen saturation ≤ 93% in resting state, 3)arterial oxygen partial pressure (PaO2) / oxygen absorption concentration (FiO2) ≤ 300MMHG, 4)pulmonary imaging shows that the focus progress > 50% in 24-48 hours
- Interstitial lung damage is judged by computed tomography.
Exclusion Criteria:
- Pregnancy, lactation and those who are not pregnant but do not take effective contraceptives measures;
- Patients with malignant tumor, other serious systemic diseases and psychosis;
- Patients who are participating in other clinical trials;
- Inability to provide informed consent or to comply with test requirements.
- Co-Infection of HIV, tuberculosis, influenza virus, adenovirus and other respiratory infection virus.
- Invasive ventilation
- Shock
- Combined with other organ failure( need organ support)
- Interstitial lung damage caused by other reasons ( in 2 weeks)
- The pulmonary imaging revealed the interstitial damage of lungs before the COVID-19 confirmed.
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:4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
---|---|
実験的:Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs)
Participants will receive standard of care plus 3 does of UC-MSCs
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3 does of UC-MSCs(4.0*10E7
cells per time) intravenously at Day 0, Day 3, Day 6.
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プラセボコンパレーター:Placebo
Participants will receive standard of care plus 3 does of placebo
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3 does of placebo(intravenously at Day 0, Day 3, Day 6)
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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 |
メジャーの説明 |
時間枠 |
---|---|---|
Change in lesion proportion (%) of full lung volume from baseline to day 28.
時間枠:Day 28
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Evaluation of Pneumonia Improvement
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Day 28
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Change in lesion proportion (%) of full lung volume from baseline to day 10 and 90
時間枠:Day 10, Day 90
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Evaluation of Pneumonia Improvement
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Day 10, Day 90
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Change in consolidation lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90.
時間枠:Day 10, Day 28, Day 90
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Evaluation of Pneumonia Improvement
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Day 10, Day 28, Day 90
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Change in ground-glass lesion proportion (%) of full lung volume from baseline to day 10, 28 and 90.
時間枠:Day 10, Day 28, Day 90
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Evaluation of Pneumonia Improvement
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Day 10, Day 28, Day 90
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Pulmonary fibrosis - related morphological features in CT scan at day 90 a. cord-like shadow b. honeycomb-like shadows c. interlobular septal thickening d. intralobular interstitial thickening e. pleural thickening
時間枠:Day 90
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Evaluation of Pneumonia Improvement
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Day 90
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Lung densitometry: Change in total voxel 'weight' in lesion area voxel 'weight'=voxel density (in HU) × voxel volume (in voxel)
時間枠:Day 10, Day 28, Day 90
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Evaluation of Pneumonia Improvement
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Day 10, Day 28, Day 90
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Lung densitometry: volumes histogram of lung density distribution (<-750, -750~-300, -300~50, >50) at day 10, 28 and 90.
時間枠:Day 10, Day 28, Day 90
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Evaluation of Pneumonia Improvement
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Day 10, Day 28, Day 90
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Time to clinical improvement in 28 days.
時間枠:Day 28
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Clinical improvement defined as a one-point deduction from baseline in a 6 ordinal scale:
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Day 28
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Oxygenation index( PaO2/FiO2)
時間枠:Day 6, Day 10, Day 28
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Evaluation of Pneumonia Improvement
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Day 6, Day 10, Day 28
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Duration of oxygen therapy(days)
時間枠:Day 28, Day 90
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Evaluation of Pneumonia Improvement
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Day 28, Day 90
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Blood oxygen saturation
時間枠:Day 6, Day 10, Day 28
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Evaluation of Pneumonia Improvement
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Day 6, Day 10, Day 28
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6-minute walk test
時間枠:Day 28, Day 90
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Evaluation of Pneumonia Improvement
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Day 28, Day 90
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Maximum vital capacity (VCmax)
時間枠:Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
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Evaluation of Pneumonia Improvement
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Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
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Diffusing Capacity (DLCO)
時間枠:Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
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Evaluation of Pneumonia Improvement
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Baseline, Day 10, Day 14, Day 21, Day 28, Day 90
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mMRC (Modified Medical Research Council) dyspnea scale
時間枠:Day 28, Day 90
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Evaluation of Pneumonia Improvement No limitation of activities, discharged from hospital =Score 1; Hospitalized, no oxygen therapy=Score 2; Oxygen by mask or nasal prongs-Score 3; Non-invasive ventilation or high-flow oxygen=Score 4; Mechanical ventilation or ECMO=Score 5; Death=Score 6. |
Day 28, Day 90
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Changes of absolute lymphocyte counts and subsets from baseline to day 6, 10, 28 and 90.
時間枠:Day 6, Day 10, Day 28, Day 90
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Marker of Immunological function
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Day 6, Day 10, Day 28, Day 90
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Changes of cytokine/chemokine levels from baseline to day 6, 10, 28 and 90.
時間枠:Day 6, Day 10, Day 28, Day 90
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Marker of Immunological function
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Day 6, Day 10, Day 28, Day 90
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Adverse events
時間枠:Day 0 through Day 90
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Safety endpoints
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Day 0 through Day 90
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Serious adverse events
時間枠:Day 0 through Day 90
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Safety endpoints
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Day 0 through Day 90
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All-cause mortality
時間枠:Day 0 through Day 90
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Safety endpoints
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Day 0 through Day 90
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協力者と研究者
スポンサー
協力者
捜査官
- スタディチェア:Fu-Sheng Wang, MD, PhD、Beijing 302 Hospital
出版物と役立つリンク
一般刊行物
- Shi L, Yuan X, Yao W, Wang S, Zhang C, Zhang B, Song J, Huang L, Xu Z, Fu JL, Li Y, Xu R, Li TT, Dong J, Cai J, Li G, Xie Y, Shi M, Li Y, Zhang Y, Xie WF, Wang FS. Human mesenchymal stem cells treatment for severe COVID-19: 1-year follow-up results of a randomized, double-blind, placebo-controlled trial. EBioMedicine. 2022 Jan;75:103789. doi: 10.1016/j.ebiom.2021.103789. Epub 2021 Dec 25.
- Shi L, Huang H, Lu X, Yan X, Jiang X, Xu R, Wang S, Zhang C, Yuan X, Xu Z, Huang L, Fu JL, Li Y, Zhang Y, Yao WQ, Liu T, Song J, Sun L, Yang F, Zhang X, Zhang B, Shi M, Meng F, Song Y, Yu Y, Wen J, Li Q, Mao Q, Maeurer M, Zumla A, Yao C, Xie WF, Wang FS. Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized, double-blind, placebo-controlled phase 2 trial. Signal Transduct Target Ther. 2021 Feb 10;6(1):58. doi: 10.1038/s41392-021-00488-5.
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
- 2020-013-D
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?
IPD プランの説明
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
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
新型コロナウイルス感染症 2019(COVID-19)の臨床試験
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AudibleHealth AI, Inc.Sunrise Research Institute; Analytical Solutions Group, Inc.; Kelley Medical Consultants LLC; R....完了コロナウイルス 病気 2019年 | SARS-CoV-2 感染症 | COVID-19 パンデミック | COVID-19 ウイルス感染 | コロナウイルス病-19 | COVID-19 ウイルス病 | 2019 新型コロナウイルス感染症 | 2019 新型コロナウイルス感染症 | 2019-nCoV 疾患アメリカ
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Leidos Life SciencesUnited States Department of Defense積極的、募集していないCOVID-19(新型コロナウイルス感染症) | COVID19 | コロナウイルス 病気 2019年 | SARS-CoV-2 感染症 | SARS-CoV-2 急性呼吸器疾患 | COVID-19 パンデミック | COVID-19 ウイルス感染 | COVID-19 ウイルス病 | 2019 新型コロナウイルス感染症 | 2019 新型コロナウイルス感染症 | 2019-nCoV 疾患 | 2019-nCoV感染アメリカ
-
Leidos Life SciencesUnited States Department of Defense引きこもったCOVID-19(新型コロナウイルス感染症) | COVID19 | コロナウイルス 病気 2019年 | SARS-CoV-2 感染症 | SARS-CoV-2 急性呼吸器疾患 | COVID-19 パンデミック | COVID-19 ウイルス感染 | COVID-19 ウイルス病 | 2019 新型コロナウイルス感染症 | 2019 新型コロナウイルス感染症 | 2019-nCoV 疾患 | 2019-nCoV感染
-
Leidos Life SciencesUnited States Department of Defense終了しましたCOVID-19(新型コロナウイルス感染症) | COVID19 | コロナウイルス 病気 2019年 | SARS-CoV2感染 | SARS-CoV-2 急性呼吸器疾患 | COVID-19 パンデミック | COVID-19 ウイルス感染 | COVID-19 ウイルス病 | 2019 新型コロナウイルス感染症 | 2019 新型コロナウイルス感染症 | 2019-nCoV 疾患 | 2019-nCoV感染アメリカ
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Janssen Vaccines & Prevention B.V.完了コロナウイルス病-2019 (COVID-19) 予防南アフリカ, ブラジル, アルゼンチン, メキシコ, インド
-
Akesobio Australia Pty Ltd完了
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Guangzhou Institute of Respiratory DiseaseTongji Hospital; Guangzhou Eighth People's Hospital; Guangzhou Cellgenes Biotechnology Co.,Ltdわからない
-
Materia Medica Holding積極的、募集していない
UC-MSCsの臨床試験
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Think Now IncorporatedUniversity of California, Berkeley; University of California, Los Angeles募集
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Göteborg UniversityWallström och Sjöbloms stiftelse; Peter Erikssons minnesfond; Back to Life完了
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Wuhan Union Hospital, ChinaWuhan Hamilton Bio-technology Co., Ltd, China.わからない
-
Puren Hospital Affiliated to Wuhan University of...Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Shanghai University; Qingdao...わからない
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Renmin Hospital of Wuhan UniversityWuhan Hamilton Biotechnology Co., Ltdわからない