Prevention of Acute Respiratory Infection in Taiwanese Institutionalized Elderly
2022년 6월 30일 업데이트: Megan Murray, MD, ScD, Harvard Medical School (HMS and HSDM)
Prevention of Acute Respiratory Infection in Taiwanese Institutionalized Elderly (PARITIE)
The purpose of this study is to assess the efficacy of Bacille Calmette-Guérin (BCG) vaccination compared to placebo against acute respiratory infections in the elderly who are less protected by standard vaccines against influenza than other age groups.
The investigators hypothesize that BCG vaccination can reduce incidence of infection and severity of a range of acute respiratory infections.
Patients who are residents of participating long-term care facilities (LTCFs), who agree to participate in the study, or with a legal guardian who agrees on their behalf, will be randomly assigned to receive BCG vaccination or a placebo.
Participants will be followed for up to six months to assess the incidence of infection and the severity of a range of acute respiratory infections.
연구 개요
상세 설명
This is a Phase III, double-blind, randomized placebo-controlled trial comparing efficacy of BCG vaccination to that of placebo in reducing severity of a range of acute respiratory infections. Participants will need to meet eligibility criteria in order to be included in the study. Those selected will be asked to provide a blood sample for complete blood count, liver function and renal tests, tests to calculate MELD score, also serological testing.
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 monitor participants' health status by using intermittent surveys about the presence of adverse events potentially related to vaccination, clinic visits or hospitalization for acute respiratory infection, BioFire® Respiratory 2.1 panel for respiratory pathogens and disease outcome status.
The investigators will screen 980 individuals to enroll 830 participants, resulting in 415 receiving BCG vaccine and 415 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 10% lost to follow-up. The number of individuals screened assumes about 15% will not be eligible to be enrolled after screening.
Objective: To measure the impact of one-time BCG-Japan vaccination on acute respiratory infections leading to hospitalization in the elderly.
Primary Endpoint 1: The cumulative incidence of hospitalization for acute respiratory infection following BCG vaccination compared to that following placebo, starting from 14 days post-vaccination, as defined using relevant ICD-10 codes.
If 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 acute respiratory infections and have added protection from disease. Identification of an intervention that can reduce the risk of infection and/or of being hospitalized with ARI would reduce the number of new cases and reducing the number of cases that require hospital admission and vast resources.
연구 유형
중재적
단계
- 2 단계
- 3단계
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
55년 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
예
연구 대상 성별
모두
설명
Inclusion Criteria:
- Clients of a long-term care facility
- 55-85 years old
Exclusion Criteria:
- Known previous or current active TB disease
- Exposure to individual with documented active TB within previous three months
- Fever (>37.5 C) within the past 24 hours
Current serious underlying medical conditions:
- HIV+
- Currently taking immunosuppressive or immunomodulatory drugs
- Expect to receive chemotherapy or radiation therapy in the coming six months, receipt of chemotherapy in the past six months or undergoing chemotherapy
- Currently on any anti-cytokine therapy
- History of organ or bone marrow transplantation
- Individual or family history of familial or acquired immune disorder, including auto-immune disorders
- Neutropenia/leukopenia (<500 neutrophils/mm3 or <400 lymphocytes/mm3)
- Chronic kidney disease (Glomerular Filtration Rate< 30 ml/min/1.73m2)
- Elevated liver enzymes (alanine aminotransferase >260 IU/L or aspartate aminotransferase >200 IU/L) or Model for End-Stage Liver Disease (MELD) score ≥30
- Treatment with oral or intravenous steroids at the time of screening, defined as daily doses of 10mg prednisone or equivalent for longer than 3 months.
- Solid or hematologic malignancy including lymphoma, leukemia and other reticuloendothelial system carcinomas within the past two years.
- Presence of Parkinson's disease
- Evidence of dermatitis at site of vaccination
- Living with someone with HIV, immunocompromised, taking immunosuppressive drugs
- Suspicion of active viral or bacterial infection, or taking antivirals or antibiotics
Any vaccine administration two weeks before or after BCG administration. For those who have received the Covid-19 vaccine, the two weeks are considered after the 2nd dose.
- Doctors in Taiwan do not always encourage the use of Covid-19 vaccination due to low incidence of disease and the risk of death due to blood clots in the only approved vaccine for use (AstraZeneca).
- Known allergy to components of the BCG vaccine or prior serious reaction to previous BCG administration
- Plan to leave the long-term care facility within the next three months
- Taking part in any ongoing trial that includes administration of an investigational product relevant to respiratory disease
- Participants with cognitive impairment whose legal guardians cannot be contacted
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 방지
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 삼루타
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: BCG Vaccine
Participants randomized to the BCG Vaccine Arm will receive the vaccine.
The vaccination site is about halfway down the outer aspect of the upper arm.
|
베이스라인에서 피내 투여된 재구성된 BCG 백신 .1mL.
|
|
위약 비교기: Placebo Arm
Placebo will be administered in an intradermal route in the same location as the BCG vaccines': upper arm.
|
.1 mL of diluent (saline) given intradermally at baseline
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
To measure the impact of one-time BCG vaccination compared to placebo in reducing the occurrence of acute respiratory infection leading to hospitalization in the elderly in Taiwan
기간: 6 months
|
Number of hospitalizations for acute respiratory infection as defined by list of ICD codes
|
6 months
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
To measure the impact of one-time BCG vaccination compared to placebo in reducing the occurrence of medically attended acute respiratory infection
기간: 6 months
|
Number of medically attended acute respiratory infection
|
6 months
|
|
To measure the impact of one-time BCG vaccination compared to placebo on microbiologically confirmed viral respiratory illness
기간: 6 months
|
Number of microbiologically confirmed viral respiratory illness by viral pathogen as measure by BioFire® Respiratory 2.1 PCR panel
|
6 months
|
|
To measure the impact of one-time BCG vaccination compared to placebo on duration of hospitalization due to acute respiratory infection during the study follow-up period
기간: 6 months
|
Total duration of days spent hospitalized due to acute respiratory infection during the study follow-up period
|
6 months
|
|
To measure the impact of one-time BCG vaccination compared to placebo on critical admissions during the follow-up period
기간: 6 months
|
Number of critical are admissions during the follow-up period
|
6 months
|
|
To measure the impact of one-time BCG vaccination compared to placebo on all-cause mortality deaths
기간: 6 months
|
Number of all-cause mortality deaths
|
6 months
|
|
To measure the impact of one-time BCG vaccination compared to placebo on local and systemic adverse events
기간: 6 months
|
Number of local and systemic adverse events to BCG vaccination following randomization
|
6 months
|
|
To measure the impact of one-time BCG vaccination compared to placebo on changes of antibody profiles
기간: 6 months
|
Number of changes in antibody profiles between enrollment and follow-up
|
6 months
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
수사관
- 수석 연구원: Megan Murray, ScD, Harvard Medical School (HMS and HSDM)
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- Mangtani P, Abubakar I, Ariti C, Beynon R, Pimpin L, Fine PE, Rodrigues LC, Smith PG, Lipman M, Whiting PF, Sterne JA. Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials. Clin Infect Dis. 2014 Feb;58(4):470-80. doi: 10.1093/cid/cit790. Epub 2013 Dec 13.
- Arts RJW, Moorlag SJCFM, Novakovic B, Li Y, Wang SY, Oosting M, Kumar V, Xavier RJ, Wijmenga C, Joosten LAB, Reusken CBEM, Benn CS, Aaby P, Koopmans MP, Stunnenberg HG, van Crevel R, Netea MG. BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity. Cell Host Microbe. 2018 Jan 10;23(1):89-100.e5. doi: 10.1016/j.chom.2017.12.010.
- Higgins JP, Soares-Weiser K, Lopez-Lopez JA, Kakourou A, Chaplin K, Christensen H, Martin NK, Sterne JA, Reingold AL. Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review. BMJ. 2016 Oct 13;355:i5170. doi: 10.1136/bmj.i5170. Erratum In: BMJ. 2017 Mar 8;356:j1241.
- Nemes E, Geldenhuys H, Rozot V, Rutkowski KT, Ratangee F, Bilek N, Mabwe S, Makhethe L, Erasmus M, Toefy A, Mulenga H, Hanekom WA, Self SG, Bekker LG, Ryall R, Gurunathan S, DiazGranados CA, Andersen P, Kromann I, Evans T, Ellis RD, Landry B, Hokey DA, Hopkins R, Ginsberg AM, Scriba TJ, Hatherill M; C-040-404 Study Team. Prevention of M. tuberculosis Infection with H4:IC31 Vaccine or BCG Revaccination. N Engl J Med. 2018 Jul 12;379(2):138-149. doi: 10.1056/NEJMoa1714021.
- Wardhana, Datau EA, Sultana A, Mandang VV, Jim E. The efficacy of Bacillus Calmette-Guerin vaccinations for the prevention of acute upper respiratory tract infection in the elderly. Acta Med Indones. 2011 Jul;43(3):185-90.
- Hatherill M, Geldenhuys H, Pienaar B, Suliman S, Chheng P, Debanne SM, Hoft DF, Boom WH, Hanekom WA, Johnson JL. Safety and reactogenicity of BCG revaccination with isoniazid pretreatment in TST positive adults. Vaccine. 2014 Jun 30;32(31):3982-8. doi: 10.1016/j.vaccine.2014.04.084. Epub 2014 May 9.
- Kleinnijenhuis J, Quintin J, Preijers F, Joosten LA, Ifrim DC, Saeed S, Jacobs C, van Loenhout J, de Jong D, Stunnenberg HG, Xavier RJ, van der Meer JW, van Crevel R, Netea MG. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17537-42. doi: 10.1073/pnas.1202870109. Epub 2012 Sep 17.
- To KK, Tsang OT, Leung WS, Tam AR, Wu TC, Lung DC, Yip CC, Cai JP, Chan JM, Chik TS, Lau DP, Choi CY, Chen LL, Chan WM, Chan KH, Ip JD, Ng AC, Poon RW, Luo CT, Cheng VC, Chan JF, Hung IF, Chen Z, Chen H, Yuen KY. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis. 2020 May;20(5):565-574. doi: 10.1016/S1473-3099(20)30196-1. Epub 2020 Mar 23.
- Netea MG, Joosten LA, Latz E, Mills KH, Natoli G, Stunnenberg HG, O'Neill LA, Xavier RJ. Trained immunity: A program of innate immune memory in health and disease. Science. 2016 Apr 22;352(6284):aaf1098. doi: 10.1126/science.aaf1098. Epub 2016 Apr 21.
- Spencer JC, Ganguly R, Waldman RH. Nonspecific protection of mice against influenza virus infection by local or systemic immunization with Bacille Calmette-Guerin. J Infect Dis. 1977 Aug;136(2):171-5. doi: 10.1093/infdis/136.2.171.
- Kleinnijenhuis J, van Crevel R, Netea MG. Trained immunity: consequences for the heterologous effects of BCG vaccination. Trans R Soc Trop Med Hyg. 2015 Jan;109(1):29-35. doi: 10.1093/trstmh/tru168.
- Ritz N, Hanekom WA, Robins-Browne R, Britton WJ, Curtis N. Influence of BCG vaccine strain on the immune response and protection against tuberculosis. FEMS Microbiol Rev. 2008 Aug;32(5):821-41. doi: 10.1111/j.1574-6976.2008.00118.x. Epub 2008 Jul 9.
- Abubakar I, Pimpin L, Ariti C, Beynon R, Mangtani P, Sterne JA, Fine PE, Smith PG, Lipman M, Elliman D, Watson JM, Drumright LN, Whiting PF, Vynnycky E, Rodrigues LC. Systematic review and meta-analysis of the current evidence on the duration of protection by bacillus Calmette-Guerin vaccination against tuberculosis. Health Technol Assess. 2013 Sep;17(37):1-372, v-vi. doi: 10.3310/hta17370.
- Walk J, de Bree LCJ, Graumans W, Stoter R, van Gemert GJ, van de Vegte-Bolmer M, Teelen K, Hermsen CC, Arts RJW, Behet MC, Keramati F, Moorlag SJCFM, Yang ASP, van Crevel R, Aaby P, de Mast Q, van der Ven AJAM, Stabell Benn C, Netea MG, Sauerwein RW. Outcomes of controlled human malaria infection after BCG vaccination. Nat Commun. 2019 Feb 20;10(1):874. doi: 10.1038/s41467-019-08659-3.
- Koeken VACM, Verrall AJ, Netea MG, Hill PC, van Crevel R. Trained innate immunity and resistance to Mycobacterium tuberculosis infection. Clin Microbiol Infect. 2019 Dec;25(12):1468-1472. doi: 10.1016/j.cmi.2019.02.015. Epub 2019 Feb 23.
- Suliman S, Geldenhuys H, Johnson JL, Hughes JE, Smit E, Murphy M, Toefy A, Lerumo L, Hopley C, Pienaar B, Chheng P, Nemes E, Hoft DF, Hanekom WA, Boom WH, Hatherill M, Scriba TJ. Bacillus Calmette-Guerin (BCG) Revaccination of Adults with Latent Mycobacterium tuberculosis Infection Induces Long-Lived BCG-Reactive NK Cell Responses. J Immunol. 2016 Aug 15;197(4):1100-1110. doi: 10.4049/jimmunol.1501996. Epub 2016 Jul 13.
- Netea MG, van Crevel R. BCG-induced protection: effects on innate immune memory. Semin Immunol. 2014 Dec;26(6):512-7. doi: 10.1016/j.smim.2014.09.006. Epub 2014 Oct 23.
- Han RF, Pan JG. Can intravesical bacillus Calmette-Guerin reduce recurrence in patients with superficial bladder cancer? A meta-analysis of randomized trials. Urology. 2006 Jun;67(6):1216-23. doi: 10.1016/j.urology.2005.12.014.
- Leentjens J, Kox M, Stokman R, Gerretsen J, Diavatopoulos DA, van Crevel R, Rimmelzwaan GF, Pickkers P, Netea MG. BCG Vaccination Enhances the Immunogenicity of Subsequent Influenza Vaccination in Healthy Volunteers: A Randomized, Placebo-Controlled Pilot Study. J Infect Dis. 2015 Dec 15;212(12):1930-8. doi: 10.1093/infdis/jiv332. Epub 2015 Jun 12.
- Kemp EB, Belshe RB, Hoft DF. Immune responses stimulated by percutaneous and intradermal bacille Calmette-Guerin. J Infect Dis. 1996 Jul;174(1):113-9. doi: 10.1093/infdis/174.1.113.
- Randomised controlled trial of single BCG, repeated BCG, or combined BCG and killed Mycobacterium leprae vaccine for prevention of leprosy and tuberculosis in Malawi. Karonga Prevention Trial Group. Lancet. 1996 Jul 6;348(9019):17-24.
- Chen Y, Li L. SARS-CoV-2: virus dynamics and host response. Lancet Infect Dis. 2020 May;20(5):515-516. doi: 10.1016/S1473-3099(20)30235-8. Epub 2020 Mar 23. No abstract available.
- Giamarellos-Bourboulis EJ, Tsilika M, Moorlag S, Antonakos N, Kotsaki A, Dominguez-Andres J, Kyriazopoulou E, Gkavogianni T, Adami ME, Damoraki G, Koufargyris P, Karageorgos A, Bolanou A, Koenen H, van Crevel R, Droggiti DI, Renieris G, Papadopoulos A, Netea MG. Activate: Randomized Clinical Trial of BCG Vaccination against Infection in the Elderly. Cell. 2020 Oct 15;183(2):315-323.e9. doi: 10.1016/j.cell.2020.08.051. Epub 2020 Sep 1.
유용한 링크
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (예상)
2022년 5월 1일
기본 완료 (예상)
2022년 7월 1일
연구 완료 (예상)
2022년 9월 1일
연구 등록 날짜
최초 제출
2021년 5월 28일
QC 기준을 충족하는 최초 제출
2021년 6월 23일
처음 게시됨 (실제)
2021년 6월 24일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2022년 7월 6일
QC 기준을 충족하는 마지막 업데이트 제출
2022년 6월 30일
마지막으로 확인됨
2022년 6월 1일
추가 정보
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. .