Prevention of Acute Respiratory Infection in Taiwanese Institutionalized Elderly

NCT04938323 | Withdrawn Phase 2 DMC

• 1 other identifier: IRB20-0661
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Acute Respiratory Infection

Outcome Measures

Primary Outcomes (1)

• 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

  Number of hospitalizations for acute respiratory infection as defined by list of ICD codes

  6 months

Secondary Outcomes (7)

• To measure the impact of one-time BCG vaccination compared to placebo in reducing the occurrence 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

  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

  6 months

• To measure the impact of one-time BCG vaccination compared to placebo on critical 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

  6 months

Study Arms (2)

BCG Vaccine

EXPERIMENTAL

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

Placebo Arm

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

BCG Vaccine DRUG

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

BCG Vaccine

Placebo DRUG

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

Placebo Arm

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clients of a long-term care facility
• years old

You may not qualify if:

• 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.

Sponsors & Collaborators

• Harvard Medical School (HMS and HSDM): lead
• Chang-Hua Hospital: collaborator

Related Publications (23)

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• 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.

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• 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.

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Related Links

• Virscan

MeSH Terms

Interventions

BCG Vaccine

Intervention Hierarchy (Ancestors)

Tuberculosis Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Megan Murray, ScD

  Harvard Medical School (HMS and HSDM)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Global Health

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

Study Record Dates

• First Submitted: May 28, 2021
• First Posted: June 24, 2021
• Study Start: May 1, 2022
• Primary Completion: July 1, 2022
• Study Completion: September 1, 2022
• Last Updated: July 6, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share