Pneumococcal conjugate vaccine trial: PNEUVAC TRIAL
| ISRCTN | ISRCTN54494731 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN54494731 |
| ClinicalTrials.gov number | NCT00371878 |
| Secondary identifying numbers | 061230 |
- Submission date
- 22/07/2005
- Registration date
- 22/07/2005
- Last edited
- 01/12/2016
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
The pneumococcus bacterium is a leading problem in HIV-infected adults. It is the leading cause of bacterial meningitis and a principal cause of bloodstream infection/blood poisoning (pneumococcal disease). HIV-infected individuals who have had one attack of serious pneumococcal infection have a 1 in 4 chance of a further attack in the next 12 months. Disease is often severe and death occurs in 20% of cases. Vaccines for preventing pneumococcal disease have been available for over 90 years, based on vaccinating with the outer lining of the bacterium, the capsule. The vaccine recommended for adults contains capsule for 23 types of pneumococci (23-valent). There are over 90 types but most disease is caused by these 23 types. Immunisation with the 23-valent vaccine was tested in HIV-infected adults in Uganda, but the vaccine failed to provide protection. A second generation of pneumococcal vaccines has been licensed for use in children. As the vaccine was developed primarily for use in children, information on the role of the vaccine in adults and particularly HIV-infected adults is lacking. The aim of this study is to test the effectiveness of the new vaccine to prevent pneumococcal disease in HIV-infected adults.
Who can participate?
Patients aged over 15 who have recovered from a serious pneumococcal infection and are willing to have an HIV test.
What does the study involve?
Participants are randomly allocated to receive either the active vaccine or a placebo (dummy) injection. The vaccination consists of two injections given into the upper arm, 4-6 weeks apart. Participants are followed–up every three months. If a participant becomes unwell they are requested to attend the Queen Elizabeth Central Hospital to be investigated for pneumococcal infection. Transport costs are provided for routine visits and those requested by the Doctor. Blood tests are carried out at routine visits and when participants are unwell – this will be 10-25 ml of blood. An HIV test is performed on the first blood sample. The results of the HIV test are available to the participants. In addition to blood tests a samples from the nose is taken at each visit to investigate for the presence of the pneumococcus in the nose.
What are the possible benefits and risks of participating?
Benefits include increased access to clinical services both for routine follow up of HIV and more rapid assessment of acute illness episodes, with greater access to diagnostic services than available routinely within the hospital. The study will encourage uptake of HIV test results with appropriate support and thereby increase access to HIV services and beneficial treatments. Risks include possible side effects from vaccination, although work to date suggests this is a very safe vaccine with low rates of reaction. There will be discomfort associated with the blood sampling and nasal swabbing, although these will be transitory. Because a great deal of research going on is HIV associated, there is the potential for individuals to be identified as HIV-infected by association with the study. Confidentiality and integration of services into routine care will minimize this risk.
Where is the study run from?
Queen Elizabeth Central Hospital, Blantyre, Malawi
When is the study starting and how long is it expected to run for?
February 2003 to October 2007
Who is funding the study?
The Wellcome Trust (UK)
Who is the main contact?
Prof. Neil French
neil.french@lshtm.ac.uk
Contact information
Scientific
Malawi-Liverpool-Wellcome Trust Labs
Blantyre
Box 3009
Malawi
| Phone | +265 (0)9 207898 |
|---|---|
| neil.french@lshtm.ac.uk |
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Investigation of the humoral immune response to pneumococcal polysaccharides and the role of a conjugate pneumococcal vaccine in secondary prevention of invasive pneumococcal disease in human immunodeficiency virus (HIV)-infected Africans |
| Study acronym | PNEUVAC |
| Study objectives | Efficacy of a seven-valent pneumococcal conjugate vaccine to prevent recurrent episodes of vaccine serotype invasive pneumococcal disease (IPD) in a primarily human immunodeficiency virus (HIV)-infected adult population. |
| Ethics approval(s) | 1. University of Malawi, College of Medicine Research and Ethics Committee, 12/01/2001, ref: P.99/00/101 2. Liverpool School of Tropical Medicine Research and Ethics Committee, 20/12/2000, ref: 00.60 |
| Health condition(s) or problem(s) studied | Invasive pneumococcal disease in HIV-infected Africans |
| Intervention | Participants are recruited from individuals who are convalescing from a known invasive pneumococcal disease event. They are randomised into two arms in a 1:1 ratio to receive two doses of vaccine one month apart. In the active arm the vaccine is Prevenar® (Wyeth pharmaceuticals seven-valent pneumococcal conjugate vaccine with a CRM carrier protein). In the control arm participants receive a matching saline placebo. Vaccine is given as a 0.5 ml injection into the non-dominant deltoid muscle. Participants are followed up at three-monthly intervals and encouraged to attend the hospital when sick for evaluation of their illness. Individuals will be followed as long as they remain alive and within the study area until the follow-up censure date which was set at 31st October 2007. Total follow up is 798 person years with a median follow up time of 1.24 years [Range 2 days to 4.66 years]. |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | |
| Phase | |
| Drug / device / biological / vaccine name(s) | |
| Primary outcome measure | Vaccine serotype invasive pneumococcal disease |
| Secondary outcome measures | 1. All invasive pneumococcal disease death 2. All cause pneumonia |
| Overall study start date | 28/02/2003 |
| Completion date | 31/10/2007 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 320 |
| Key inclusion criteria | 1. Confirmed case of IPD discharged from hospital 2. Resident of Blantyre and its immediately neighbouring districts 3. Willing to attend Queen Elizabeth Central Hospital (QECH) when sick 4. Aged over 15 years, either sex 5. Willing to have HIV testing performed on stored serum |
| Key exclusion criteria | 1. Pregnancy 2. Previous pneumococcal vaccine 3. Active acute systemic illness - following recovery participant may be recruited 4. Past hypersensitivity reaction to vaccination 5. Bed-ridden or life expectancy judged to be less than three months |
| Date of first enrolment | 28/02/2003 |
| Date of final enrolment | 31/05/2007 |
Locations
Countries of recruitment
- Malawi
Study participating centre
Box 3009
Malawi
Sponsor information
University/education
Senate House
Research Support
Abercromby Square
Liverpool
L69 3BX
England
United Kingdom
| Website | http://www.liv.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/04xs57h96 |
Funders
Funder type
Charity
Private sector organisation / International organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 04/03/2010 | Yes | No | |
| Results article | results | 01/09/2016 | Yes | No |
Editorial Notes
01/12/2016: Publication reference added.
03/02/2016: Plain English summary added.
14/02/2007: The overall trial end date was changed from 31/03/2006 to 31/10/2007.
