- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT04288102
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
연구 개요
상태
상세 설명
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.
연구 유형
등록 (실제)
단계
- 2 단계
연락처 및 위치
연구 장소
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Hubei
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Wuhan, Hubei, 중국, 430000
- General Hospital of Central Theater Command
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Wuhan, Hubei, 중국, 430000
- Maternal and Child Hospital of Hubei Province
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Wuhan, Hubei, 중국, 430000
- Wuhan Huoshenshan Hospital
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 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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위약 비교기: 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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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Change in lesion proportion (%) of full lung volume from baseline to day 28.
기간: Day 28
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Evaluation of Pneumonia Improvement
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Day 28
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Change in lesion proportion (%) of full lung volume from baseline to day 10 and 90
기간: 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.
기간: 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.
기간: 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
기간: 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)
기간: 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.
기간: 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.
기간: 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)
기간: 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)
기간: 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
기간: 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
기간: 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)
기간: 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)
기간: 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
기간: 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.
기간: 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.
기간: 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
기간: 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
기간: 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
기간: Day 0 through Day 90
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Safety endpoints
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Day 0 through Day 90
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공동 작업자 및 조사자
협력자
수사관
- 연구 의자: Fu-Sheng Wang, MD, PhD, Beijing 302 Hospital
간행물 및 유용한 링크
일반 간행물
- 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.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 2020-013-D
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
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AudibleHealth AI, Inc.Sunrise Research Institute; Analytical Solutions Group, Inc.; Kelley Medical Consultants LLC 그리고 다른 협력자들완전한코로나바이러스 질병 2019 | SARS-CoV-2 감염 | 코로나19 감염병 세계적 유행 | COVID-19 바이러스 감염 | 코로나바이러스 질병-19 | COVID-19 바이러스 질병 | 2019 신종 코로나바이러스 감염증 | 2019 신종 코로나바이러스 감염증 | 2019-nCoV 질병미국
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Leidos Life SciencesUnited States Department of Defense모집하지 않고 적극적으로코로나바이러스감염증-19 : 코로나19 | 코로나19 | 코로나바이러스 질병 2019 | SARS-CoV-2 감염 | SARS-CoV-2 급성 호흡기 질환 | 코로나19 감염병 세계적 유행 | COVID-19 바이러스 감염 | COVID-19 바이러스 질병 | 2019 신종 코로나바이러스 감염증 | 2019 신종 코로나바이러스 감염증 | 2019-nCoV 질병 | 2019-nCoV 감염미국
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Leidos Life SciencesUnited States Department of Defense빼는코로나바이러스감염증-19 : 코로나19 | 코로나19 | 코로나바이러스 질병 2019 | SARS-CoV-2 감염 | SARS-CoV-2 급성 호흡기 질환 | 코로나19 감염병 세계적 유행 | COVID-19 바이러스 감염 | COVID-19 바이러스 질병 | 2019 신종 코로나바이러스 감염증 | 2019 신종 코로나바이러스 감염증 | 2019-nCoV 질병 | 2019-nCoV 감염
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Leidos Life SciencesUnited States Department of Defense종료됨코로나바이러스감염증-19 : 코로나19 | 코로나19 | 코로나바이러스 질병 2019 | SARS-CoV2 감염 | SARS-CoV-2 급성 호흡기 질환 | 코로나19 감염병 세계적 유행 | COVID-19 바이러스 감염 | COVID-19 바이러스 질병 | 2019 신종 코로나바이러스 감염증 | 2019 신종 코로나바이러스 감염증 | 2019-nCoV 질병 | 2019-nCoV 감염미국
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Janssen Vaccines & Prevention B.V.완전한코로나바이러스 질병-2019(COVID-19) 예방남아프리카, 브라질, 아르헨티나, 멕시코, 인도
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Akesobio Australia Pty Ltd완전한
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Guangzhou Institute of Respiratory DiseaseTongji Hospital; Guangzhou Eighth People's Hospital; Guangzhou Cellgenes Biotechnology Co...알려지지 않은
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Fundacion Clinica Valle del LiliUniversidad Autonoma de Occidente완전한COVID-19 폐렴 | COVID-19(코로나바이러스 질병 2019)콜롬비아
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Materia Medica Holding모집하지 않고 적극적으로
UC-MSCs에 대한 임상 시험
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Beijing 302 HospitalLanZhou University; Chinese PLA General Hospital; Renmin Hospital of Wuhan University; Shanghai... 그리고 다른 협력자들아직 모집하지 않음
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Ruijin HospitalCellular Biomedicine Group Ltd.완전한
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Universitas SriwijayaDr. Mohammad Hoesin Central General Hospital완전한
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Ruijin HospitalCellular Biomedicine Group Ltd.알려지지 않은
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Chinese Academy of SciencesThe Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School완전한
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Think Now IncorporatedUniversity of California, Berkeley; University of California, Los Angeles모병
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Institute of Hematology & Blood Diseases Hospital모집하지 않고 적극적으로