Severe Acute Malnutrition in Childhood, Pneumococcal Disease, Pneumococcal Vaccines, Pneumococcal Infection, Pneumonia in Children
Conditions
Keywords
Pneumococcal, Severe Acute Malnutrition in childhood, Pneumococcal vaccine, Pneumosil, Pneumococcal disease, Pneumococcal infection, Pneumonia
Brief summary
The goal of the OPTIMAL clinical trial is to learn if a dose of a pneumococcal conjugate vaccine (PCV) generates a good immune response in young children who are in hospital with severe acute malnutrition. Researchers will compare an intervention group who get a dose of a PCV (Pneumosil) to a control group who get a dose of a Typhoid conjugate vaccine (Typbar TCV). To ensure all participants receive timely potential benefits, at 3 months participants in the intervention group with receive a dose of Typbar TCV, and those in the conrol group will receive a dose of Pneumosil. Participants will be visited 4 times at their homes over six months after vaccination, with a phone review at 12 months after vaccination.
Detailed description
This is a prospective, single-centre, double-blind, randomised controlled trial in 264 children aged 6-59 months hospitalised with severe acute malnutrition. Participants will be randomised (1:1) to receive either a dose of a pneumococcal conjugate vaccine (Pneumosil, the intervention group) or a dose of a Typhoid conjugate vaccine (Typbar TCV, the control group). Stratification for randomisation will be done on (a) prior immunisation with a PCV (confirmed or unknown/unvaccinated); and (b) severity of malnurition (weight-for-height/length z-score \<-4 or \>=-4). Participants will be enrolled as soon as practical after admission to hospital, while randomisation and vaccine administration will occur once the participant is medically stable in the 'transition phase' of SAM care. The primary objective is to demonstrate that immune responses to the 10 pneumococcal serotypes in Pneumosil are better in participants who receive Pneumosil, compared to those who receive Typbar TCV, when measured 28 days after vaccination.
Interventions
BIOLOGICALPneumococcal conjugate vaccine
10-valent pneumococcal polysaccharide conjugate vaccine at a dosage of 2μg for each serotype polysaccharide for 1, 5, 6A, 7F, 9V, 14, 19A, 19F, 23F, and 4μg for serotype 6B, conjugated to a carrier protein (CRM197), polysorbate 20 and aluminium phosphate as an adjuvant. Administered as an intramuscular injection of 0.5mL.
BIOLOGICALTyphoid conjugate vaccine
Typhoid conjugate vaccine at a dosage of 25μg purified Vi capsular polysaccharide of Salmonella typhi Ty2 conjugated to Tetanus Toxoid with preservative (2-Phenoxyethanol). Administered as an intramuscular injection of 0.5mL.
Sponsors
Murdoch Childrens Research Institute
The University of Western Australia
University of Edinburgh
Timor-Leste Ministry of Health
Nick Fancourt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
A prospective, single-centre, double-blind, phase 4, randomised, controlled trial in children aged 6-59 months hospitalised with severe acute malnutrition.
Eligibility
Sex/Gender
ALL
Age
6 Months to 59 Months
Healthy volunteers
No
Inclusion criteria
1. Aged 6-59 months at the time of hospitalisation 2. Hospitalised with severe acute malnutrition (SAM, defined as any one of a, b, or c): 1. weight-for-length/height z-score \<-3; or 2. middle upper arm circumference \<11.5cm; or 3. bilateral pitting pedal oedema unexplained by other causes 3. Parent/carer is willing for their child to participate in the study and has provided written informed consent 4. Parent/carer is willing to comply with all study procedures outlined in the protocol, including specimen collection, for the duration of the study
Exclusion criteria
1. Known history of allergy or hypersensitivity to any component of either study vaccine, including diphtheria toxoid, or a history of anaphylactic shock. 2. Treatment with another investigational drug or other intervention in the 30 days prior to randomisation, or ongoing participation in another clinical trial. 3. Suspected primary or secondary immunodeficiency or prolonged administration (\>14 days) of an immune modifying drug (including oral glucocorticoids) in the past 3 months. 4. Known terminal illness expected to result in death within 6 months. 5. Participants who, in the opinion of the site Principal Investigator, are unable to comply with the study protocol, including scheduled visits, assessments, and any other protocol-required procedures. 6. Previously enrolled in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serotype-specific immunoglobulin G (IgG) antibodies | 4 weeks after vaccination | Pneumosil serotype-specific (1, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F, 23F) immunoglobulin G (IgG) geometric mean concentrations (GMCs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with serotype-specific IgG antibody responses ≥ 0.35 μg/mL | 4 weeks and 3 months after vaccination | Proportion of participants with Pneumosil serotype-specific IgG concentrations ≥ 0.35μg/mL |
| Functional antibody responses | 4 weeks and 3 months after vaccination | Pneumosil serotype-specific pneumococcal geometric mean opsonisation indices (GMOIs) |
| Salivary IgG antibodies | 4 weeks and 3 months after vaccination | Serotype-specific salivary IgG (μg/ml) for Pneumosil serotypes and non-vaccine types 3, 4, 11A, and 18C |
| Salivary immunoglobulin A (IgA) antibodies | 4 weeks and 3 months after vaccination | Serotype-specific salivary IgA (μg/ml) for Pneumosil serotypes and non-vaccine types 3, 4, 11A, and 18C |
| Nasopharyngeal carriage of pneumococcus | 3 months after vaccination | Proportion of participants with nasopharyngeal carriage of Pneumosil vaccine-type pneumococci and their antimicrobial resistance patterns |
| Serotype-specific IgG antibodies | 4 weeks and 3 months after vaccination | Pneumosil serotype-specific IgG GMCs |
| Re-hospitalisation | 3 months and 12 months after vaccination | Any repeat admission to hospital as confirmed by medical records |
| Mortality | 3 and 12 months after vaccination | Deaths as reported. Cause of death determined from review of medial records. |
| Composite illness or mortality | Reviewed at all study visits until completion (12 months after vaccination) | Repeat hospitalisation(s) or death. |
| Salmonella Typhi antibodies | 4 weeks and 3 months after vaccination for all participants, plus 4 months and 6 months after vaccination for participants in the control arm | Proportion of paticipants with \>4 fold rise (compared to pre-vaccination) of Salmonella Typhi anti-Vi IgG geometric mean titres (GMTs) |
| Severe acute malnutrition recovery | Reviewed at all study visits until completion (12 months after vaccination) | Weight-for-height/length z-score \>= -2 or MUAC \>12.5cm |
Countries
Timor-Leste
Contacts
Primary ContactNicholas S. S. Fancourt, PhD
Backup ContactJane N Nelson, Bachelor of Nursing
Outcome results
None listed