Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000999033
Ethics application status
Not yet submitted
Date submitted
3/06/2010
Date registered
17/11/2010
Date last updated
17/11/2010
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of pneumococcal conjugate vaccine in preventing acquisition and carriage of pneumococcal vaccine serotypes in Tanzanian children with human immunodeficiency virus/ acquired immunodeficiency syndrome (HIV/AIDS)
Scientific title
Efficacy of pneumococcal conjugate vaccine in preventing acquisition and carriage of pneumococcal vaccine serotypes in Tanzanian children withhuman immunodeficiency virus/ acquired immunodeficiency syndrome (HIV/AIDS)
Secondary ID [1] 252065 0
Nil
Universal Trial Number (UTN)
U1111-1115-4400
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pneumococcal disease 257515 0
HIV/AIDS 257603 0
Condition category
Condition code
Public Health 257675 257675 0 0
Epidemiology
Infection 257778 257778 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pneumococcal vaccination
1
a) containing two microgram of Pneumococcal polysaccharide
serotypes 4, 9V, 14, 18C, 19F, 23F, and four micrograms of pneumococcal polysaccharide serotype 6B. It also contains sodium chloride and water for injections.
b) two identical vaccines will be administered three months apart.
c) administered as a intramuscular injection
2
At the fourth visit to the clinic children will be given the first dose of the vaccine they have not yet received. That is children will be given four vaccinations over nine months. Firstly two doses of either control or intervention vaccine then two doses of the other vaccine in succession. There is three months between the final dose of the first type of vaccine and the first dose of the second, there is not usually a wash out in these studies. Children will be randomly allocated to receive control or treatment vaccine first. All children in the study will receive both vaccines only the order will vary.
Intervention code [1] 256609 0
Prevention
Comparator / control treatment
Control vaccine Haemophilus influenzae (Hib) (Act-HIB(registered trademark)- Aventis Pasteur
Quadrace)
1
a) contains Pertussis Vaccine Combined with Diphtheria and Tetanus Toxoids combinedwith Inactivated Poliomyelitis Vaccine, the solution contains 0.6% +/- 0.1%2-phenoxyethanol as preservative
b) two identical vaccines will be administered three months apart.
c) administered as a intramuscular injection
2
At the fourth visit to the clinic children will be given the first dose of the vaccine they have not yet received. That is children will be given four vaccinations over nine months. Firstly two doses of either control or intervention vaccine then two doses of the other vaccine. Children will be randomly allocated to receive control or treatment vaccine first. All children in the study will receive both vaccines only the order will vary.
Control group
Active

Outcomes
Primary outcome [1] 258579 0
Nasopharyngeal carriage of vaccine serotypes.

A nasopharyngeal swab will be obtained at the 0, 3, 6 and 9-month visit, prior to administration of the vaccine dose. Samples will be collected and processed according to the WHO working group standard methods for detecting upper respiratory carriage of S. pneumoniae and the WHO Laboratory Manual for the Diagnosis of Meningitis Caused by Neisseria meningitidis, S. pneumoniae, and H. influenzae. A paediatric calcium alginate tipped aluminium swab will be inserted through the nose into the nasopharynx, and rotated gently through 180 degrees. The swab will be placed into 1ml of Skim milk tryptone-glucose-glycerin (STGG) transport medium, made according to WHO methods.

Swabs will then be taken directly to the laboratory where they will be frozen at minus 70C until culture. Culturing will take place on 5g/ml gentamicin in sheeps blood agar.

20l of the sample will be streaked onto a plate, incubated at 35C in CO2 for two days, using a candle jar, as pneumococcus grows best under anaerobic conditions. Any samples that showing growth will then be subcultured up to four times, depending on how many colonies are present. Samples are then subcultured onto blood agar.

Facilities for serotyping are currently not available in Tanzania. Samples will be serotyped at the Kenya Medical Research Institute (KMRI) in Kilifi in Kenya by Quellung reaction. PCR serotyping at Westmead Hospital in Australia, will give us information on multiple serotype carriage.
Timepoint [1] 258579 0
0, 3, 6 and 9 months
Secondary outcome [1] 264447 0
Antibody response to vaccination If blood has been taken for other serologic tests then any sera left over, with the permission of the patient and parents, will be placed in EDTA tubes and frozen at -20 degrees Celsius. It will be transferred to CIDM laboratories at Westmead hospital for enzyme-linked immunosorbent assay tests to measure antibody response to the vaccine.
Timepoint [1] 264447 0
0, 3, 6 and 9 months

Eligibility
Key inclusion criteria
HIV positive children aged 1-14 years old
Minimum age
1 Years
Maximum age
14 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous vaccination

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
HIV-positive children will be recruited when they present for routine follow-up to the clinic (usually every 1 to 3 months) and also when presenting with an illness. During each visit to The Diana Centre, they will be assessed for their need of treatment. Medical care will be provided according to national guidelines. Patients with severe disease or requiring urgent care will be transferred to the appropriate area in the hospital where this will be provided.
The following procedures will be performed:
ascertain participant eligibility,
explain the purpose of the study,
obtain written informed consent for study participation
complete the case report form
obtain and process a nasopharyngeal swab,
vaccinate the participant,
record epidemiological and treatment information from notes.
Only children with a written informed consent form, signed/thumb-printed by parents/guardians will be screened.

Participant eligibility will be ascertained through a checklist. Then the parent/guardian of the child will be requested to read the Kiswahili (local language) information sheet and informed consent form or these will be read to them. If informed consent to participate is provided, data will be collected through interview and from the patient’s medical notes. Information will be recorded in a standardised Case Report Form (CRF). The CRF is designed to investigate baseline data, such as presenting symptoms, HIV-history, socio-economic status and prophylactic and therapeutic medications. Height and weight will be measured by standard methods using calibrated scales.

As participants are recruited they will be allocated to the infant group (less than five years) or the school aged group (greater than or equal to five years). Random numbers will be generated via Excel these will then be put into brown security envelopes and stored in a file. An envelope will be taken from the file. Depending on whether this contains odd or an even number they will be assigned to receiving PCV or Hib as the first 2 doses.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
As participants are recruited they will be allocated to the infant group (less than five years) or the school aged group (greater than or equal to five years). Random numbers will be generated via specific statistical software these will then be put into brown security envelopes and stored in a file. An envelope will be taken from the file. Depending on whether this contains odd or an even number they will be assigned to receiving pneumococcal conjugate vaccine (PCV) or Hib as the first 2 doses.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
216
Accrual to date
Final
Recruitment outside Australia
Country [1] 2681 0
Tanzania, United Republic Of
State/province [1] 2681 0
Muheza

Funding & Sponsors
Funding source category [1] 257102 0
Self funded/Unfunded
Name [1] 257102 0
Prof Robert Booy
Country [1] 257102 0
Australia
Primary sponsor type
Individual
Name
Prof Robert Booy
Address
National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases (NCIRS)
The Children's Hospital at Westmead Cnr Hawkesbury Rd & Hainsworth St, Westmead
Post: Locked Bag 4001, Westmead NSW 2145, Australia
T: +61 2 9845 1433
F: +61 2 9845 1418
Country
Australia
Secondary sponsor category [1] 256362 0
None
Name [1] 256362 0
Address [1] 256362 0
Country [1] 256362 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 259135 0
Ethics committee address [1] 259135 0
Ethics committee country [1] 259135 0
Date submitted for ethics approval [1] 259135 0
18/05/2010
Approval date [1] 259135 0
Ethics approval number [1] 259135 0

Summary
Brief summary
This is a randomised controlled trial of a pneumococcal conjugate vaccine to examine the efficacy of this vaccine in preventing the nasopharyngeal acquisition and carriage of vaccine serotypes of pneumococcus, among Tanzanian children with HIV/AIDS. Prevention of nasopharyngeal carriage can be used as a surrogate for vaccine protective efficacy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31257 0
Address 31257 0
Country 31257 0
Phone 31257 0
Fax 31257 0
Email 31257 0
Contact person for public queries
Name 14504 0
Prof Robert Booy
Address 14504 0
National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases
The Children's Hospital at Westmead Cnr Hawkesbury Rd & Hainsworth St, Westmead
Post: Locked Bag 4001, Westmead NSW 2145, Australia

T: +61 2 9845 1433
F: +61 2 9845 1418
Country 14504 0
Australia
Phone 14504 0
+61 2 9845 1415
Fax 14504 0
Email 14504 0
[email protected]
Contact person for scientific queries
Name 5432 0
Prof Robert Booy
Address 5432 0
National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases
The Children's Hospital at Westmead Cnr Hawkesbury Rd & Hainsworth St, Westmead
Post: Locked Bag 4001, Westmead NSW 2145, Australia

T: +61 2 9845 1433
F: +61 2 9845 1418
Country 5432 0
Australia
Phone 5432 0
+61 2 9845 1415
Fax 5432 0
Email 5432 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseImmunogenicity and Efficacy of Pneumococcal Conjugate Vaccine (Prevenar13) in Preventing Acquisition of Carriage of Pneumococcal Vaccine Serotypes in Tanzanian Children With HIV/AIDS.2021https://dx.doi.org/10.3389/fimmu.2021.673392
N.B. These documents automatically identified may not have been verified by the study sponsor.