Prevention of Acute Respiratory Infection in Taiwanese Institutionalized Elderly

Sponsor

Harvard Medical School (HMS and HSDM) (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04938323

Collaborator

Chang-Hua Hospital (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Respiratory Infection	Drug: BCG Vaccine Drug: Placebo	Phase 2/Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants will be randomized in a 1:1 allocation to receive intradermal administration of BCG vaccination or placebo.Participants will be randomized in a 1:1 allocation to receive intradermal administration of BCG vaccination or placebo.

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

Participants and investigators will be blinded. Designated staff whose responsibility will be to administer the BCG vaccine or placebo will not be blinded. These designated staff members will not be involved in the collection of outcome data

Primary Purpose:

Prevention

Official Title:

Prevention of Acute Respiratory Infection in Taiwanese Institutionalized Elderly (PARITIE)

Anticipated Study Start Date :

May 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Sep 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: BCG Vaccine .1 mL of reconstituted BCG vaccine given intradermally at baseline.
Placebo Comparator: Placebo Arm Placebo will be administered in an intradermal route in the same location as the BCG vaccines': upper arm.	Drug: Placebo .1 mL of diluent (saline) given intradermally at baseline

Arm

Intervention/Treatment

Experimental: 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.

Drug: BCG Vaccine

.1 mL of reconstituted BCG vaccine given intradermally at baseline.

Placebo Comparator: Placebo Arm

Placebo will be administered in an intradermal route in the same location as the BCG vaccines': upper arm.

Drug: Placebo

.1 mL of diluent (saline) given intradermally at baseline

Outcome Measures

Primary Outcome Measures

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 [6 months]
Number of hospitalizations for acute respiratory infection as defined by list of ICD codes

Secondary Outcome Measures

To measure the impact of one-time BCG vaccination compared to placebo in reducing the occurrence of medically attended acute respiratory infection [6 months]
Number of medically attended acute respiratory infection
To measure the impact of one-time BCG vaccination compared to placebo on microbiologically confirmed viral respiratory illness [6 months]
Number of microbiologically confirmed viral respiratory illness by viral pathogen as measure by BioFire® Respiratory 2.1 PCR panel
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 [6 months]
Total duration of days spent hospitalized due to acute respiratory infection during the study follow-up period
To measure the impact of one-time BCG vaccination compared to placebo on critical admissions during the follow-up period [6 months]
Number of critical are admissions during the follow-up period
To measure the impact of one-time BCG vaccination compared to placebo on all-cause mortality deaths [6 months]
Number of all-cause mortality deaths
To measure the impact of one-time BCG vaccination compared to placebo on local and systemic adverse events [6 months]
Number of local and systemic adverse events to BCG vaccination following randomization
To measure the impact of one-time BCG vaccination compared to placebo on changes of antibody profiles [6 months]
Number of changes in antibody profiles between enrollment and follow-up

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Harvard Medical School (HMS and HSDM)
Chang-Hua Hospital

Investigators

Principal Investigator: Megan Murray, ScD, Harvard Medical School (HMS and HSDM)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Virscan

Publications

Responsible Party:

Megan Murray, MD, ScD, Professor of Global Health, Harvard Medical School (HMS and HSDM)

ClinicalTrials.gov Identifier:

NCT04938323

Other Study ID Numbers:

IRB20-0661

First Posted:

Jun 24, 2021

Last Update Posted:

Jul 6, 2022

Last Verified:

Jun 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Infections

Communicable Diseases

Respiratory Tract Infections

BCG Vaccine

Study Results

No Results Posted as of Jul 6, 2022