Condition category
Respiratory
Date applied
13/09/2005
Date assigned
25/01/2006
Last edited
05/11/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://hisdu2.sph.uq.edu.au/arivac/

Contact information

Type

Scientific

Primary contact

Dr Marilla Lucero

ORCID ID

Contact details

Research Institute for Tropical Medicine (RITM)
Research Drive
Filinvest Corporate City
Alabang
Muntinlupa City
1781
Philippines
+63 (0)2 807 2634
mglucero@pldtdsl.net

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

PNF13399

Study information

Scientific title

Acronym

ARIVAC

Study hypothesis

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

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.

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Prevention

Patient information sheet

Condition

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 names

Primary outcome measures

Radiologically confirmed, community-acquired pneumonia at least 14 days after the third dose of the study vaccine in first 2 years of life.

Secondary outcome measures

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

Overall trial start date

05/07/2000

Overall trial end date

18/12/2004

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

12,190

Participant 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

Recruitment start date

05/07/2000

Recruitment end date

18/12/2004

Locations

Countries of recruitment

Philippines

Trial participating centre

Research Institute for Tropical Medicine (RITM)
Muntinlupa City
1781
Philippines

Sponsor information

Organisation

ARIVAC Consortium (Finland)

Sponsor details

National Public Health Institute (Kansanterveyslaitos)
Mannerheimintie 166
Helsinki
00300
Finland
+358 (0)947 448749
hanna.nohynek@ktl.fi

Sponsor type

Other

Website

http://www.sph.uq.edu.au/arivac

Funders

Funder type

Other

Funder name

National Health and Medical Research Council (NHMRC) (Australia)

Alternative name(s)

NHMRC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Australia

Funder name

European Commission (Belgium) - DG Research, INCO Programme

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Finnish Academy (Finland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Finnish Ministry of Foreign Affairs (Finland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Physicians for Social Responsibility (PSR) (Finland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Program for Appropriate Technology and Health (PATH) (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Global Alliance for Vaccines, Accelerated Development and Implementation Plan (GAVI ADIP Pnc) (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Provincial Government of Bohol (Philippines)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Local government units of Tagbilaran City, Dauis, Panglao, Balilihan, Cortez and Baclayon (Philippines)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Research Institute for Tropical Medicine (RITM) (Philippines)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

National Public Health Institute (KTL) (Finland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

University of Colorado (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

University of Queensland (Australia)

Alternative name(s)

UQ

Funding Body Type

private sector organisation

Funding Body Subtype

academic

Location

Australia

Funder name

Sanofi Pasteur (France)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18644109
2. 2012 evaluation in http://www.ncbi.nlm.nih.gov/pubmed/22676626

Publication citations

  1. Results

    Puumalainen T, Quiambao B, Abucejo-Ladesma E, Lupisan S, Heiskanen-Kosma T, Ruutu P, Lucero MG, Nohynek H, Simoes EA, Riley I, , Clinical case review: a method to improve identification of true clinical and radiographic pneumonia in children meeting the World Health Organization definition for pneumonia., BMC Infect. Dis., 2008, 8, 95, doi: 10.1186/1471-2334-8-95.

  2. Evaluation

    Sanvictores DH, Lucero MG, Nohynek H, Tallo VL, Tanskanen A, Nillos LT, Williams G, , The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines., BMC Res Notes, 2012, 5, 274, doi: 10.1186/1756-0500-5-274.

Additional files

Editorial Notes