Ignite Creation Date:
2025-12-24 @ 7:38 PM
Ignite Modification Date:
2025-12-29 @ 5:14 AM
Study NCT ID:
NCT04534803
Status:
WITHDRAWN
Last Update Posted:
2021-06-28
First Post:
2020-08-21
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
BCG Against Covid-19 for Prevention and Amelioration of Severity Trial (BAC to the PAST)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000086382', 'term': 'COVID-19'}], 'ancestors': [{'id': 'D011024', 'term': 'Pneumonia, Viral'}, {'id': 'D011014', 'term': 'Pneumonia'}, {'id': 'D012141', 'term': 'Respiratory Tract Infections'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D018352', 'term': 'Coronavirus Infections'}, {'id': 'D003333', 'term': 'Coronaviridae Infections'}, {'id': 'D030341', 'term': 'Nidovirales Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D001500', 'term': 'BCG Vaccine'}], 'ancestors': [{'id': 'D032581', 'term': 'Tuberculosis Vaccines'}, {'id': 'D001428', 'term': 'Bacterial Vaccines'}, {'id': 'D014612', 'term': 'Vaccines'}, {'id': 'D001688', 'term': 'Biological Products'}, {'id': 'D045424', 'term': 'Complex Mixtures'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Participants and investigators and designated staff whose responsibility will be to administer the BCG vaccine or placebo will be blinded.'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Participants will be randomized in a 1:1 allocation to receive intradermal administration of BCG vaccination or placebo.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': 'At this time it has been decided by the study team the the study will no longer take place in the United States.', 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2021-09', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-06', 'completionDateStruct': {'date': '2022-07', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2021-06-23', 'studyFirstSubmitDate': '2020-08-21', 'studyFirstSubmitQcDate': '2020-08-29', 'lastUpdatePostDateStruct': {'date': '2021-06-28', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-09-01', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-05', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'To assess the efficacy of BCG vaccination compared to placebo in reducing severe Covid-19 disease among elderly residents of skilled nursing facilities.', 'timeFrame': '12 months', 'description': 'Number of people diagnosed with severe Covid-19 disease as documented in the electronic heath record; severe Covid-19 disease is defined as any instance of death, hospitalization, or non-hospitalization but requiring new administration of supplemental oxygen or having a decline in oxygen saturation of 10%, change from ambulant to non-ambulant for 3 or more days, or any new change in mental health status.'}], 'secondaryOutcomes': [{'measure': 'To assess the efficacy of BCG vaccination compared to placebo in reducing the following among elderly residents of skilled nursing facilities (by number of cases)', 'timeFrame': '12 months', 'description': '1. Number of cases of any COVID-19 disease, defined as a positive SARS-Cov-2 test (per PCR or serology), plus fever (as documented in EHR) or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (as documented in EHR.)\n2. Number of cases of asymptomatic SARS-CoV-2 infection, defined as evidence of SARS-CoV-2 infection (by PCR or seroconversion), absence of associated respiratory illness (as documented in EHR), and no evidence of exposure prior to randomization (baseline serology will be negative).\n3. Number of cases of critical care admissions with SARS-CoV-2, defined as the number of admissions to critical care associated with a positive SARS-CoV-2 test.\n4. Number of cases of critical care admission duration with SARS-CoV-2, defined as the number of days admitted to critical care (using medical/hospital records) associated with a positive SARS-CoV-2 test.'}, {'measure': 'To assess the efficacy of BCG vaccination compared to placebo in reducing the following among elderly residents of skilled nursing facilities (by number of cases), continued', 'timeFrame': '12 months', 'description': '5\\. Number of cases of critical care admissions, defined as the number of admissions to critical care.\n\n6\\. Number of cases of mechanical ventilation with SARS-CoV-2, defined as the number of participants needing mechanical ventilation (as documented by EHR) and associated with a positive SARS-CoV-2 test.\n\n7\\. Number of cases of mechanical ventilation, defined as the number of participants needing mechanical ventilation.\n\n8\\. Number of cases of All-Cause Mortality, defined as death reported by the long-term care facility.\n\n9\\. Number of cases of any fever or respiratory illness, defined as fever (as documented in EHR), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (as documented in EHR).'}, {'measure': 'To assess the efficacy of BCG vaccination compared to placebo in reducing the following among elderly residents of skilled nursing facilities (by number of episodes)', 'timeFrame': '12 months', 'description': '1. Number of episodes of fever or respiratory illness, defined as fever (as documented in EHR), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (as documented in EHR).\n2. Number of episodes of any COVID-19 disease, defined as a positive SARS-Cov-2 test (per PCR or serology), plus fever (as documented in EHR) or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (as documented in EHR.)\n3. Number of episodes of local and systemic adverse events to BCG vaccination measured over the 3 months following randomization (type and severity of local and systemic adverse events will be collected and graded using toxicity grading scale).'}, {'measure': 'To assess the efficacy of BCG vaccination compared to placebo in reducing the following among elderly residents of skilled nursing facilities (by number of days)', 'timeFrame': '12 months', 'description': '1. Number of days of symptom duration of fever or respiratory illness, defined as number of days with symptoms in any episode of illness that meets the case definition for fever or respiratory illness, defined as fever (as documented in EHR), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (as documented in EHR).\n2. Number of days of COVID-19 symptom duration, defined as the number of days with symptoms in any episode of illness that meets the case definition for any COVID-19 disease.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Covid19']}, 'referencesModule': {'references': [{'pmid': '32031570', 'type': 'BACKGROUND', 'citation': 'Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.'}, {'pmid': '32167524', 'type': 'BACKGROUND', 'citation': 'Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934-943. doi: 10.1001/jamainternmed.2020.0994.'}, {'pmid': '32217556', 'type': 'BACKGROUND', 'citation': 'Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, Ma K, Xu D, Yu H, Wang H, Wang T, Guo W, Chen J, Ding C, Zhang X, Huang J, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020 Mar 26;368:m1091. doi: 10.1136/bmj.m1091.'}, {'pmid': '32191259', 'type': 'BACKGROUND', 'citation': 'Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX, Chong M, Lee M. Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA. 2020 Apr 28;323(16):1612-1614. doi: 10.1001/jama.2020.4326.'}, {'pmid': '32239127', 'type': 'BACKGROUND', 'citation': 'Cao J, Tu WJ, Cheng W, Yu L, Liu YK, Hu X, Liu Q. Clinical Features and Short-term Outcomes of 102 Patients with Coronavirus Disease 2019 in Wuhan, China. Clin Infect Dis. 2020 Jul 28;71(15):748-755. doi: 10.1093/cid/ciaa243.'}, {'pmid': '32310612', 'type': 'BACKGROUND', 'citation': 'Basu-Ray I, Almaddah NK, Vaqar S, Soos MP. Cardiac Manifestations of Coronavirus (COVID-19). 2024 Feb 12. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. 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Epub 2006 Jan 13.'}, {'pmid': '17372194', 'type': 'BACKGROUND', 'citation': 'Brosch R, Gordon SV, Garnier T, Eiglmeier K, Frigui W, Valenti P, Dos Santos S, Duthoy S, Lacroix C, Garcia-Pelayo C, Inwald JK, Golby P, Garcia JN, Hewinson RG, Behr MA, Quail MA, Churcher C, Barrell BG, Parkhill J, Cole ST. Genome plasticity of BCG and impact on vaccine efficacy. Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5596-601. doi: 10.1073/pnas.0700869104. Epub 2007 Mar 19.'}, {'pmid': '31677386', 'type': 'BACKGROUND', 'citation': 'Schaltz-Buchholzer F, Bjerregaard-Andersen M, Oland CB, Golding C, Stjernholm EB, Monteiro I, Aaby P, Benn CS. Early Vaccination With Bacille Calmette-Guerin-Denmark or BCG-Japan Versus BCG-Russia to Healthy Newborns in Guinea-Bissau: A Randomized Controlled Trial. 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Japanese.'}, {'pmid': '19788832', 'type': 'BACKGROUND', 'citation': 'Jou R, Huang WL, Su WJ. Tokyo-172 BCG vaccination complications, Taiwan. Emerg Infect Dis. 2009 Sep;15(9):1525-6. doi: 10.3201/eid1509.081336. No abstract available.'}, {'pmid': '19008268', 'type': 'BACKGROUND', 'citation': 'Hawkridge A, Hatherill M, Little F, Goetz MA, Barker L, Mahomed H, Sadoff J, Hanekom W, Geiter L, Hussey G; South African BCG trial team. Efficacy of percutaneous versus intradermal BCG in the prevention of tuberculosis in South African infants: randomised trial. BMJ. 2008 Nov 13;337:a2052. doi: 10.1136/bmj.a2052.'}, {'pmid': '9987142', 'type': 'BACKGROUND', 'citation': 'Guerin N, Teulieres L, Noba A, Schlumberger M, Bregere P, Chauvin P. Comparison of the safety and immunogenicity of the lyophilized Merieux seed and the World Health Organization working reference BCG vaccines in school-aged children in Senegal. 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Epub 2008 Dec 12.'}, {'pmid': '26015500', 'type': 'BACKGROUND', 'citation': 'Totura AL, Whitmore A, Agnihothram S, Schafer A, Katze MG, Heise MT, Baric RS. Toll-Like Receptor 3 Signaling via TRIF Contributes to a Protective Innate Immune Response to Severe Acute Respiratory Syndrome Coronavirus Infection. mBio. 2015 May 26;6(3):e00638-15. doi: 10.1128/mBio.00638-15.'}, {'pmid': '32085846', 'type': 'BACKGROUND', 'citation': 'Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. No abstract available.'}, {'pmid': '32132681', 'type': 'BACKGROUND', 'citation': 'Netea MG, Dominguez-Andres J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, Joosten LAB, van der Meer JWM, Mhlanga MM, Mulder WJM, Riksen NP, Schlitzer A, Schultze JL, Stabell Benn C, Sun JC, Xavier RJ, Latz E. Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020 Jun;20(6):375-388. doi: 10.1038/s41577-020-0285-6. Epub 2020 Mar 4.'}, {'pmid': '29328910', 'type': 'BACKGROUND', 'citation': 'Mitroulis I, Ruppova K, Wang B, Chen LS, Grzybek M, Grinenko T, Eugster A, Troullinaki M, Palladini A, Kourtzelis I, Chatzigeorgiou A, Schlitzer A, Beyer M, Joosten LAB, Isermann B, Lesche M, Petzold A, Simons K, Henry I, Dahl A, Schultze JL, Wielockx B, Zamboni N, Mirtschink P, Coskun U, Hajishengallis G, Netea MG, Chavakis T. Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity. Cell. 2018 Jan 11;172(1-2):147-161.e12. doi: 10.1016/j.cell.2017.11.034.'}], 'seeAlsoLinks': [{'url': 'https://coronavirus.jhu.edu/map.html', 'label': 'Related Info'}, {'url': 'https://data.cms.gov/stories/s/COVID-19-Nursing-Home-Data/bkwz-xpvg', 'label': 'Covid-19 Nursing Home Data'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to assess the efficacy of Bacille Calmette-Guérin (BCG) vaccination compared to placebo in reducing severe Covid-19 disease among elderly residents of skilled nursing facilities. The investigators hypothesize that BCG vaccination can reduce severity of Covid-19 disease. Patients who are residents of participating long-term care facilities (LTCFs), with the ability to understand and cooperate with study procedures, who agree to participate in the study will be randomly assigned to receive BCG vaccination or a placebo. Participants will be followed for up to twelve months to assess severity of Covid-19 outcomes.', 'detailedDescription': "This is a Phase III, double-blind, randomized placebo-controlled trial comparing efficacy of BCG vaccination to that of placebo in reducing severity of Covid-19. Participants will need to meet eligibility criteria in order to be included in the study. Those selected, will be asked to provide a blood or saliva sample for Covid-19 serological test and an Interferon gamma release assay (IGRA) test for tuberculosis infection, only if IGRA or tuberculin skin test (TST) result is not available from the previous year. Participants will be randomized in a 1:1 allocation to receive intradermal administration of BCG vaccination or placebo at baseline. During follow-up, the study team will extract participants information from nursing home records regarding Covid-19-like symptoms, diagnosis, outcomes, as well as any adverse side effects of BCG vaccination. At 6 and 12 months of follow up, an additional blood or saliva sample will be collected to perform a Covid-19 serological test.\n\nThe investigators will screen 2,500 individuals to enroll 2,100 participants, resulting in 1,050 receiving BCG vaccine and 1,050 receiving placebo. The proposed enrollment sample size is designed to provide 80% power to detect 60% vaccine efficacy (a relative risk of 0.4 among the vaccinated) with 0.05 type-1 error in a two-tailed test, assuming a Covid-19 attack rate of 10% in elderly NH and 38.5% severe Covid-19 among the infected patients, and a design effect = 1.2, and 15% lost during the 6-month follow-up. The number of individuals screened assumes about 20% will not be eligible/agree to be enrolled.\n\nNote that the 60% vaccine efficacy was based on the observed three-fold decline in respiratory infections in the adolescent cohort.\n\nObjective: To assess the efficacy of BCG vaccination compared to placebo in reducing severe Covid-19 disease among elderly residents of skilled nursing facilities.\n\nPrimary Endpoint 1: Cases of Covid-19 disease classified as severe. Severe COVID-19 disease will be defined as: COVID-19 disease with hospitalization, death, or non-hospitalized severe disease where non-hospitalized severe disease is defined as a change in status including administration of new supplemental oxygen or decline in oxygen saturation of 10%; change from ambulant to non-ambulant status of 3+ days; new change in mental status as documented in the electronic health record\n\nThe investigators will use the Cox proportional-hazards model to calculate hazard ratios for the development of severe Covid-19 between the BCG and placebo arms.\n\nIf BCG vaccine is shown to be effective in this age group, it will be of major benefit to both study participants and other elderly individuals at risk for infection and disease from Covid-19. With no other vaccine alternative currently available, an efficacy of even 50% could reduce the death rate among infected patients accordingly. BCG has been reported to have a variety of other possible benefits including reduction in the risk of TB disease, Alzheimer's Disease and reduction in other respiratory infection. Because these benefits have not been proven in clinical trials, they will not be presented to potential participants."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['OLDER_ADULT'], 'minimumAge': '70 Years', 'healthyVolunteers': True, 'eligibilityCriteria': "Inclusion:\n\n* Residents of a participating LTCF\n* 70 years or older\n* Ability to understand and cooperate with study procedures including dressing care.\n\n * Nursing home staff or the research team will ensure participants are correctly doing dressing care.\n\nExclusion:\n\n* Previous or current SARS-CoV2 infection/Covid-19 disease defined by documentation of disease in clinical chart or positive PCR test.\n* Previous or known active TB disease\n* Does not have an established proxy or guardian, but has cognitive impairment that would prohibit the participant from fully understanding the extent of study requirements and risks, or prohibit their ability to provide informed consent.\n* Obesity (Body Mass Index \\[BMI\\] \\> 35)\n* Fever (\\>38 C) within the past 24 hours\n* Current or historic serious underlying medical conditions:\n\n * HIV+\n * History of organ or bone marrow transplantation\n * History of major immunodeficiency disorder\n * Active solid or hematologic malignancy diagnosed within the past two years\n * Presence of significant neurologic disease, eg. Alzheimer's disease\n* Receipt of any of the following drugs:\n\n * Currently taking immunosuppressive or immunomodulatory drugs (inhalers and/or prednisone are acceptable to take)\n\n * The Prednisone doses equivalent \\> 2 mg/kg or \\> 20 mg per day of prednisone administered for \\>/= 2 weeks are immunosuppressive and should be avoided with live vaccines.\n * Expect to receive chemotherapy in the coming six months, receipt of chemotherapy in the past six months or undergoing chemotherapy\n * Currently on any anti-cytokine therapy\n * Taking metformin treatment\n * Suspicion of active viral or bacterial infection\n * Plan to leave the nursing home within the next 6 months\n * Taking part in another intervention-based trial for Covid-19\n * Allergy to any component of the BCG vaccine or an anaphylactic or allergic reaction to a previous dose of BCG vaccination"}, 'identificationModule': {'nctId': 'NCT04534803', 'briefTitle': 'BCG Against Covid-19 for Prevention and Amelioration of Severity Trial (BAC to the PAST)', 'organization': {'class': 'OTHER', 'fullName': 'Harvard Medical School (HMS and HSDM)'}, 'officialTitle': 'Bacillus Calmette-Guerin Against Covid-19 for Prevention and Amelioration of Severity Trial', 'orgStudyIdInfo': {'id': 'IRB20-1243'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'BCG Vaccine', 'description': 'Participants randomized to the BCG arm will receive BCG vaccine. The vaccination site is about halfway down the outer aspect of the upper arm.', 'interventionNames': ['Drug: BCG Vaccine']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo Arm', 'description': 'Placebo will be administered in an intradermal route in the same location as the BCG vaccines: upper arm.', 'interventionNames': ['Other: Placebo']}], 'interventions': [{'name': 'BCG Vaccine', 'type': 'DRUG', 'description': '.1 mL of reconstituted BCG vaccine given intradermally at baseline.', 'armGroupLabels': ['BCG Vaccine']}, {'name': 'Placebo', 'type': 'OTHER', 'description': '.1 nL of diluent (saline) given intradermally at baseline', 'armGroupLabels': ['Placebo Arm']}]}, 'contactsLocationsModule': {'overallOfficials': [{'name': 'Megan B Murray, MD, ScD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Harvard Medical School (HMS and HSDM)'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Harvard Medical School (HMS and HSDM)', 'class': 'OTHER'}, 'collaborators': [{'name': 'Texas Medical Research Associates, L.L.C.', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Ronda Stryker and William Johnston Professor of Global Health', 'investigatorFullName': 'Megan Murray, MD, ScD', 'investigatorAffiliation': 'Harvard Medical School (HMS and HSDM)'}}}}