Effectiveness of an eleven-valent pneumococcal (type 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) conjugate vaccine against pneumonia in Philippine children: A double-blind, placebo-controlled, randomised, multicentre, effectiveness study

ISRCTN	ISRCTN62323832
DOI	https://doi.org/10.1186/ISRCTN62323832
Protocol serial number	PNF13399
Sponsor	ARIVAC Consortium (Finland)
Funders	National Health and Medical Research Council (NHMRC) (Australia), European Commission (Belgium) - DG Research, INCO Programme, Finnish Academy (Finland), Finnish Ministry of Foreign Affairs (Finland), Physicians for Social Responsibility (PSR) (Finland), Program for Appropriate Technology and Health (PATH) (USA), Global Alliance for Vaccines, Accelerated Development and Implementation Plan (GAVI ADIP Pnc) (Switzerland), Provincial Government of Bohol (Philippines), Local government units of Tagbilaran City, Dauis, Panglao, Balilihan, Cortez and Baclayon (Philippines), Research Institute for Tropical Medicine (RITM) (Philippines), National Public Health Institute (KTL) (Finland), University of Colorado (USA), University of Queensland (Australia), Sanofi Pasteur (France)

Submission date: 13/09/2005
Registration date: 25/01/2006
Last edited: 05/11/2012

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Marilla Lucero
Scientific

Research Institute for Tropical Medicine (RITM)
Research Drive
Filinvest Corporate City
Alabang
Muntinlupa City
1781
Philippines

Phone	+63 (0)2 807 2634
Email	mglucero@pldtdsl.net

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	ARIVAC
Study objectives	Primary objective: The vaccine is efficacious in preventing community-acquired X-ray positive pneumonia. The minimum efficacy, estimated by the lower limit of the 95% confidence interval, is 15%. The relative risk of the X-ray positive pneumonia in the vaccine group is less than 0.85 when compared to the placebo group. Objective 2a: Hypothesis: The vaccine is efficacious in preventing community-acquired pneumonia requiring hospitalization. The relative risk of pneumonia is lower than one when compared to the placebo group; in other words, the vaccine efficacy is higher than 0%. Objective 2b: Hypothesis: The vaccine is efficacious in preventing community-acquired pneumonia not requiring hospitalization. The relative risk of pneumonia is lower than one when compared to the placebo group; in other words, the vaccine efficacy is higher than 0%. Objective 2c: Hypothesis: The vaccine is efficacious in preventing culture proven vaccine type-specific invasive pneumococcal disease. The relative risk of culture proven vaccine type-specific invasive pneumococcal disease is lower than one when compared to the placebo group; in other words, the vaccine efficacy is higher than 0%. Objective 2d: Hypothesis: The eleven-valent pneumococcal conjugate vaccine is safe when administered concomitantly with the vaccines of Expanded Programmes on Immunization (EPI) and Hib vaccine. For the nested carriage and immunogenicity study: Objective 2e: Hypothesis: Children immunized with the eleven-valent pneumococcal vaccine have higher concentrations of antipneumococcal polysaccharide antibodies and higher opsonophagocytic activity in comparison to the placebo recipients. Objective 2f: Hypothesis: Significantly fewer children immunized with the eleven-valent pneumococcal conjugate vaccine will carry vaccine serotypes of Streptococcus pneumoniae than the placebo recipients.
Ethics approval(s)	The Technical Review Board and Ethical Review Board (Institutional Review Board [IRB]) of the Research Institute for Tropical Medicine (RITM), Philippines, reviewed and approved the original study protocol in 1999. A counterpart ethical review committee at the National Public Health Institute in Finland likewise reviewed the study protocol, and approved it in the same year. The RITM IRB evaluated yearly the progress of the study and gave its corresponding approval to proceed with the conduct of the trial. The latest approval was awarded on August 8, 2005.
Health condition(s) or problem(s) studied	Pediatric pneumococcal pneumonia, sepsis, meningitis.
Intervention	Study Vaccine Group: An eleven-valent pneumococcal tetanus-diphtheria toxoid conjugated vaccine, diphtheria-tetanus-pertussis whole cell vaccine, Haemophilus influenzae type b vaccine, hepatitis B vaccine, oral polio vaccine, measles vaccine according to national immunization program schedule. Control (Placebo) Vaccine Group: Saline (NaCl), diphtheria-tetanus-pertussis whole cell vaccine, Haemophilus influenzae type b vaccine, hepatitis B vaccine, oral polio vaccine, measles vaccine according to national immunization program.
Intervention type	Biological/Vaccine
Phase	Phase III
Drug / device / biological / vaccine name(s)
Primary outcome measure(s)	Radiologically confirmed, community-acquired pneumonia at least 14 days after the third dose of the study vaccine in first 2 years of life.
Key secondary outcome measure(s)	Secondary outcomes: World Health Organisation (WHO) Pneumonia 1.1. Any episode of community-acquired pneumonia requiring or not requiring hospitalization 1.2. Any episode of community-acquired pneumonia requiring hospitalization 2. Any episode of community-acquired pneumonia not requiring hospitalization 3. Any episode of culture proven invasive pneumococcal disease, determined as vaccine-specific serotype, vaccine-related serotype, vaccine serogroup, or non-vaccine serotype or group of Streptococcus pneumoniae 4. Safety of the 11PCV when administered concomitantly with the EPI and Hib vaccines 5. Reactogenicity of the 11PCV after each injection 6. Immunogenicity and the opsonophagocytic activity (OPA) of the 11PCV in 11PCV and placebo recipients 7. Nasopharyngeal carriage of vaccine and non-vaccine specific serotypes of Streptococcus pneumoniae in 11PCV and placebo recipients
Completion date	18/12/2004

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	6 Weeks
Upper age limit	6 Months
Sex	All
Target sample size at registration	12190
Key inclusion criteria	For the effectiveness study and the nested immunogenicity study: 1. Any child who comes for routine vaccination to a barangay health station in the 48 barangays in the six municipalities of Bohol, the Philippines (i.e. Baclayon, Balilihan, Cortes, Dauis, Panglao and Tagbilaran) 2. Considered to be in good health on the basis of medical history and observation taken at the barangay health station 3. At least 6 weeks of age and not older than 6 months of age 4. Having at least one parent or other legal representative giving their informed consent attested by signature For the effectiveness study: Is a resident of any of the barangays within the catchment of the 45 barangay health stations of the six municipalities for at least the past 3 months with his/her family, or intends to stay permanently For the nested immunogenicity, safety and carriage study: Is a resident of any of the barangays within the catchment of the three chosen barangay health stations (i.e. Dampas-Tagbilaran, Danao and Main Health Center-Panglao) for at least the past 3 months with his/her family, or intends to stay permanently
Key exclusion criteria	For the effectiveness study and the nested immunogenicity study: Any child who: 1. Has received the first dose of diphtheria, tetanus, pertussis (DTP) vaccine 2. Has acute febrile illness (rectal temperature >/= 38.5°C) at the time of inclusion 3. Is suspected to have a neurological disease (a contraindication to the DTP vaccine) 4. Has history of hospitalization for and/or treatment for immune suppression 5. Is enrolled or scheduled to be enrolled in another clinical trial
Date of first enrolment	05/07/2000
Date of final enrolment	18/12/2004

Locations

Countries of recruitment

Philippines

Study participating centre

Research Institute for Tropical Medicine (RITM)

Muntinlupa City
1781
Philippines

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	21/07/2008		Yes	No
Other publications	evaluation	07/06/2012		Yes	No
Study website	Study website	11/11/2025	11/11/2025	No	Yes