Ignite Creation Date:
2024-05-05 @ 11:47 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00131794
Status:
COMPLETED
Last Update Posted:
2016-09-02
First Post:
2005-08-18
Brief Title:
Bacillus Calmette-Guerin BCG Vaccine and Morbidity From Malaria
Sponsor:
London School of Hygiene and Tropical Medicine
Organization:
London School of Hygiene and Tropical Medicine
Study Overview
Official Title:
The Effect of BCG Vaccine on Morbidity From Malaria
Status:
COMPLETED
Status Verified Date:
2005-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
BCG vaccine is given at or shortly after birth in many developing countries to prevent tuberculosis In Guinea Bissau it has been shown that its protective effect against death is greater than would be expected from its effect against tuberculosis This observation suggests that BCG may enhance the ability of the immune system of young children to make a protective response to other infections including malaria There is some evidence to support this hypothesis as BCG protects against malaria in experimental animals
Because BCG is a recommended vaccine a randomised controlled trial of BCG at birth would not be ethically justifiable However it is not known whether re-vaccination with BCG in the second year of life might provide some added benefit and a large study to determine this is under way in Guinea Bissau This study examined the effect of re-vaccination with BCG on the incidence of clinical malaria If re-vaccination with BCG at 19 months of age is found to protect against malaria this would support the hypothesis that one of the ways that BCG at birth provides protection to young children is through an effect on malaria
Because BCG is a recommended vaccine a randomised controlled trial of BCG at birth would not be ethically justifiable However it is not known whether re-vaccination with BCG in the second year of life might provide some added benefit and a large study to determine this is under way in Guinea Bissau This study examined the effect of re-vaccination with BCG on the incidence of clinical malaria If re-vaccination with BCG at 19 months of age is found to protect against malaria this would support the hypothesis that one of the ways that BCG at birth provides protection to young children is through an effect on malaria
Detailed Description:
Background
Studies undertaken in Guinea Bissau have shown that the protective effect of BCG vaccine against death in young children is greater than would be expected from its effect in preventing tuberculosis How this might be achieved is not known but BCG could act by enhancing the immune response to common infections including malaria which is an important cause of death in young children in Bissau There is some laboratory evidence to support this hypothesis BCG prevents malaria in rodents probably by activating their reticulo-endothelial system and Freunds adjuvant an emulsion of tubercle bacilli in oil prevents malaria in primates
In most developing countries BCG is given as soon as possible after birth and is an integral part of the immunisation programme so that a controlled trial which withheld neonatal BCG vaccination would not be ethical However it is uncertain how long the non-specific protective effect of BCG persists and whether this could be sustained by a further injection of BCG in the second year of life A major trial to investigate this possibility is under way in Guinea Bissau with mortality as its main end-point The current study has made use of this opportunity to investigate whether or not re-vaccination with BCG has a protective effect against malaria
Objective
The primary objective of the study was to determine if re-vaccination with BCG reduced morbidity from malaria in young children
Study area
The study was carried out within the area covered by the Bandim Health Project in Bissau the capital of Guinea Bissau West Africa The study area within the suburbs of Bissau has a population of approximately 70000 who are under demographic surveillance Routine infant immunisations are given at 3 health centers in the area babies who deliver in the national hospital are given BCG before they leave Overall coverage with BCG is high 95
Study population
All infants resident in the study area were eligible for inclusion in the main BCG re-vaccination trial Children were recruited to the malaria sub-study during the period January to October 2003 at the age of 19 months when they were due to receive BCG re-vaccination or to remain as a control Separate written informed consent was obtained for inclusion in the malaria sub-study
Study procedure
At the age of 19 months children whose parents gave consent were allocated randomly to receive BCG revaccination or to be a control and entered into the malaria study Because BCG leaves a scar it was not possible to undertake a double blinded study However the field staff who assessed the patients for clinical attacks of malaria were unaware of the hypothesis underlying the trial and blood films were read without knowledge of an individuals study group
The prevalence of malaria in children in the two groups was determined through a combination of active and passive surveillance Any child in the study who presented to one of the dispensaries in the study area or to the national hospital with an illness suggestive of malaria was investigated for possible malaria If a child had a history of fever or a raised axillary temperature 375 degrees Celsius blood films were obtained and the hemoglobin measured Children found to have malaria were treated with chloroquine which was the first line treatment at the time of the study In addition to passive surveillance two cross sectional surveys of all children in the study were undertaken at the beginning and at the end of the malaria transmission season during which blood films were collected and the hemoglobin measured Quality control for the reading of blood films was provided by staff of the MRC Laboratories The Gambia
Some of the study children with clinical malaria were enrolled in a separate case control study of risks for malaria
Trial end-point
The primary trial end-point was the incidence of malaria in children in the two study groups Malaria was defined as the presence of a fever or a history of feverb no other obvious cause for the fever and c the presence of asexual stage Plasmodium falciparum asexual parasitemia of any density For a second definition a parasite density of 5000 parasites per ul or the estimated fever threshold for the study area was required
Sample size
On the basis of previous experience in the study area it was estimated that the incidence of malaria in children in the control group would be about 03 attacks during the malaria transmission season On this basis a study with 600 children in each arm would have 80 power at the 5 level of significance to detect a reduction in the incidence of malaria of 25 in the children who received BCG A trial of this size would have 80 power to detect a reduction in the prevalence of parasitaemia of 22 at the final cross-sectional survey assuming a prevalence in the control arm of 35 asexual P falciparum parasitemia an assumption based on the results of a previous survey
Monitoring
A Data Safety and Monitoring Board DSMB provided supervision for the study and approved the analytical plan before the trial code was broken Monitoring visits were made by scientists from the UK and from The Gambia
Studies undertaken in Guinea Bissau have shown that the protective effect of BCG vaccine against death in young children is greater than would be expected from its effect in preventing tuberculosis How this might be achieved is not known but BCG could act by enhancing the immune response to common infections including malaria which is an important cause of death in young children in Bissau There is some laboratory evidence to support this hypothesis BCG prevents malaria in rodents probably by activating their reticulo-endothelial system and Freunds adjuvant an emulsion of tubercle bacilli in oil prevents malaria in primates
In most developing countries BCG is given as soon as possible after birth and is an integral part of the immunisation programme so that a controlled trial which withheld neonatal BCG vaccination would not be ethical However it is uncertain how long the non-specific protective effect of BCG persists and whether this could be sustained by a further injection of BCG in the second year of life A major trial to investigate this possibility is under way in Guinea Bissau with mortality as its main end-point The current study has made use of this opportunity to investigate whether or not re-vaccination with BCG has a protective effect against malaria
Objective
The primary objective of the study was to determine if re-vaccination with BCG reduced morbidity from malaria in young children
Study area
The study was carried out within the area covered by the Bandim Health Project in Bissau the capital of Guinea Bissau West Africa The study area within the suburbs of Bissau has a population of approximately 70000 who are under demographic surveillance Routine infant immunisations are given at 3 health centers in the area babies who deliver in the national hospital are given BCG before they leave Overall coverage with BCG is high 95
Study population
All infants resident in the study area were eligible for inclusion in the main BCG re-vaccination trial Children were recruited to the malaria sub-study during the period January to October 2003 at the age of 19 months when they were due to receive BCG re-vaccination or to remain as a control Separate written informed consent was obtained for inclusion in the malaria sub-study
Study procedure
At the age of 19 months children whose parents gave consent were allocated randomly to receive BCG revaccination or to be a control and entered into the malaria study Because BCG leaves a scar it was not possible to undertake a double blinded study However the field staff who assessed the patients for clinical attacks of malaria were unaware of the hypothesis underlying the trial and blood films were read without knowledge of an individuals study group
The prevalence of malaria in children in the two groups was determined through a combination of active and passive surveillance Any child in the study who presented to one of the dispensaries in the study area or to the national hospital with an illness suggestive of malaria was investigated for possible malaria If a child had a history of fever or a raised axillary temperature 375 degrees Celsius blood films were obtained and the hemoglobin measured Children found to have malaria were treated with chloroquine which was the first line treatment at the time of the study In addition to passive surveillance two cross sectional surveys of all children in the study were undertaken at the beginning and at the end of the malaria transmission season during which blood films were collected and the hemoglobin measured Quality control for the reading of blood films was provided by staff of the MRC Laboratories The Gambia
Some of the study children with clinical malaria were enrolled in a separate case control study of risks for malaria
Trial end-point
The primary trial end-point was the incidence of malaria in children in the two study groups Malaria was defined as the presence of a fever or a history of feverb no other obvious cause for the fever and c the presence of asexual stage Plasmodium falciparum asexual parasitemia of any density For a second definition a parasite density of 5000 parasites per ul or the estimated fever threshold for the study area was required
Sample size
On the basis of previous experience in the study area it was estimated that the incidence of malaria in children in the control group would be about 03 attacks during the malaria transmission season On this basis a study with 600 children in each arm would have 80 power at the 5 level of significance to detect a reduction in the incidence of malaria of 25 in the children who received BCG A trial of this size would have 80 power to detect a reduction in the prevalence of parasitaemia of 22 at the final cross-sectional survey assuming a prevalence in the control arm of 35 asexual P falciparum parasitemia an assumption based on the results of a previous survey
Monitoring
A Data Safety and Monitoring Board DSMB provided supervision for the study and approved the analytical plan before the trial code was broken Monitoring visits were made by scientists from the UK and from The Gambia
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None