Ignite Creation Date:
2024-05-05 @ 11:48 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00131703
Status:
COMPLETED
Last Update Posted:
2017-01-12
First Post:
2005-08-18
Brief Title:
Efficacy and Safety of Sulphadoxine-pyrimethamine and Amodiaquine in Ghanaian Pregnant Women
Sponsor:
London School of Hygiene and Tropical Medicine
Organization:
London School of Hygiene and Tropical Medicine
Study Overview
Official Title:
A Randomised Double Blind Clinical Trial of Amodiaquine AQ and Sulphadoxine-pyrimethamine SP Used Singly and in Combination AQSP Compared With Chloroquine CQ in the Treatment of Falciparum Malaria Infection in Pregnancy
Status:
COMPLETED
Status Verified Date:
2017-01
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:
Malaria in pregnancy is potentially fatal to both the mother and the foetus particularly in the primigravidae Implementation of appropriate control and preventive measures is challenged by the fact that malaria infection in pregnancy is often asymptomatic and parasitized red blood cells sequestrated in the placental microcirculation may not be detectable in the peripheral blood In addition the widespread prevalence of parasites resistant to chloroquine and sulphadoxine-pyrimethamine SP and the safety concerns about newer antimalarials poverty and inadequate supply have made antimalarial treatment options available to pregnant women very limited These have necessitated an urgent search for alternative safe and efficacious treatment options for pregnant women The objective of this study is to assess the efficacy safety and tolerability of four antimalarial treatment options in rural Ghana within a programme setting
Detailed Description:
Primary objective
To determine the effect of AQ SP and the AQSP combination compared with CQ treatment on the prevalence of peripheral parasitaemia on days 14 and 28 post treatment
Secondary objectives
1 To compare the incidence of adverse events in the treatment groups
2 To compare the effect of study drugs on maternal haemoglobin on 14 and 28 days post treatment and at delivery
3 To compare the effect of study drugs on peripheral and placental parasite densities at delivery
4 To compare the effect of study drugs on birth weight at delivery
5 To assess the effect modifications of gestational age parity gravidity prior antimalarial use presence or absence of symptoms at enrolment baseline parasite density and baseline Hb on the parasitological and haematological responses to the test drugs
6 To assess the accuracy of the OptiMAL antigen test for detecting peripheral parasitaemia compared to microscopy
7 To compare the overall incidence of adverse pregnancy outcomes abortion stillbirth congenital abnormality prematurity and intrauterine deaths in the study group to local rates obtained from St Theresas Hospitals records
Study location and population
The study was carried out at the St Theresas Hospital in the Nkoranza district of the Brong Ahafo Region of Ghana The St Theresas hospital is a general district hospital It has a bed capacity of 80 and provides all basic medical services including adult medicine paediatrics surgery and obstetrics and gynaecology The study enrolled pregnant women of all parities attending the St Theresas Hospitals antenatal clinic with a gestational age of 16 weeks and above between March 2003 and September 2004
Methods
Antennal screening and enrolment
All pregnant women who attended antenatal clinics were screened for malaria antigens with OptiMAL dipsticks Those with a positive antigen test were considered eligible and after informed consent had been obtained from them 5mls of venous blood was drawn from an antecubital vein for baseline measurements of haemoglobin white blood cell counts total and differential bilirubin alanine aminotransferase aspartate aminotransferase and gamma-glutamyl transferase and for making filter paper blood spots Women were then assessed clinically and obstetrically with the view to enrolling them into the study Pregnancy viability and gestational age were confirmed with ultrasound scanning by the study clinician or the principal investigator Pregnant women with positive malaria antigen tests confirmed microscopically were randomised into four treatment arms if they satisfied all inclusion criteria
Follow-up schedule
Field workers visited the study women in their homes following the initial supervised drug administration at the antenatal clinic on post treatment days 3 7 14 and 28 and performed the following routines
Day 3 and Day 7 Obtained venous blood for filter paper blood spots white cell and malaria parasite counts and recorded any side effects
Day 14 and Day 28 Obtained venous blood for white cell and malaria parasite count measurement of alanine and aspartate transaminases bilirubin and for filter paper blood spots and recorded any side effects
Subsequently pregnant women were seen at the antenatal clinic monthly and for those with 32 weeks and above of gestation fortnightly At these visits they were actively screened for peripheral parasitaemia using OptiMAL dipstick test At any time before delivery if the test was negative the woman remained on daily haematinics If women who were already enrolled had positive antigen test confirmed by microscopy they received another course of the treatment they were initially assigned to Women were enrolled in the study only for the first episode of malaria detected during the antenatal visit At delivery midwives recorded birth weights and any stillbirths perinatal deaths or congenital abnormalities They also made slides from peripheral placental and cord blood and sampled maternal blood for haemoglobin measurements Any record of a congenital deformity was verified and confirmed by a clinician The women and their babies were visited at home at six weeks post delivery to record any neonatal adverse events such as deaths or severe morbidity
Outcome measures
Primary
1 Prevalence of parasitaemia on days 14 and 28 post treatment
Secondary
1 Incidence of adverse drug events within seven days following treatment
2 Proportions of pregnant women withdrawn from the study due to the occurrence of adverse drug events clinical and laboratory by day 7 following initiation of treatment
3 Change in maternal haemoglobin concentrations at days 14 and 28 following treatment
4 Prevalence of peripheral parasitaemia at delivery
5 Prevalence of placental parasitaemia at delivery
6 Proportions of abnormal biochemistry and white blood cell values on days 14 and 28 post treatment
7 Sensitivity specificity positive and negative predictive values likelihood ratios and the area under receiver operating characteristic ROC curve for the OptiMAL antigen test
8 Incidences of adverse pregnancy outcomes in the study group
9 Prevalence of postpartum parasitaemia
10 Prevalence of postpartum anaemia
Sample Size
This was based on the assumption of a 28-day parasitological clearance of 90 for AQ SP and the AQSP combination and 78 for chloroquine α 5 power 90 Allowing for a 15 loss to follow-up 225 pregnant women were recruited into each of the 4 treatment arms of the study giving a total study size of 900 pregnant women
Data and safety monitoring board
A data and safety monitoring board DSMB was constituted for the project The board was responsible for
Regular monitoring of the data and safety issues concerned with the study
Reviewing the PIs reports on serious adverse events and making recommendations on further progress of the study
Reviewing the statistical analysis plan prior to breaking the study drug codes
To determine the effect of AQ SP and the AQSP combination compared with CQ treatment on the prevalence of peripheral parasitaemia on days 14 and 28 post treatment
Secondary objectives
1 To compare the incidence of adverse events in the treatment groups
2 To compare the effect of study drugs on maternal haemoglobin on 14 and 28 days post treatment and at delivery
3 To compare the effect of study drugs on peripheral and placental parasite densities at delivery
4 To compare the effect of study drugs on birth weight at delivery
5 To assess the effect modifications of gestational age parity gravidity prior antimalarial use presence or absence of symptoms at enrolment baseline parasite density and baseline Hb on the parasitological and haematological responses to the test drugs
6 To assess the accuracy of the OptiMAL antigen test for detecting peripheral parasitaemia compared to microscopy
7 To compare the overall incidence of adverse pregnancy outcomes abortion stillbirth congenital abnormality prematurity and intrauterine deaths in the study group to local rates obtained from St Theresas Hospitals records
Study location and population
The study was carried out at the St Theresas Hospital in the Nkoranza district of the Brong Ahafo Region of Ghana The St Theresas hospital is a general district hospital It has a bed capacity of 80 and provides all basic medical services including adult medicine paediatrics surgery and obstetrics and gynaecology The study enrolled pregnant women of all parities attending the St Theresas Hospitals antenatal clinic with a gestational age of 16 weeks and above between March 2003 and September 2004
Methods
Antennal screening and enrolment
All pregnant women who attended antenatal clinics were screened for malaria antigens with OptiMAL dipsticks Those with a positive antigen test were considered eligible and after informed consent had been obtained from them 5mls of venous blood was drawn from an antecubital vein for baseline measurements of haemoglobin white blood cell counts total and differential bilirubin alanine aminotransferase aspartate aminotransferase and gamma-glutamyl transferase and for making filter paper blood spots Women were then assessed clinically and obstetrically with the view to enrolling them into the study Pregnancy viability and gestational age were confirmed with ultrasound scanning by the study clinician or the principal investigator Pregnant women with positive malaria antigen tests confirmed microscopically were randomised into four treatment arms if they satisfied all inclusion criteria
Follow-up schedule
Field workers visited the study women in their homes following the initial supervised drug administration at the antenatal clinic on post treatment days 3 7 14 and 28 and performed the following routines
Day 3 and Day 7 Obtained venous blood for filter paper blood spots white cell and malaria parasite counts and recorded any side effects
Day 14 and Day 28 Obtained venous blood for white cell and malaria parasite count measurement of alanine and aspartate transaminases bilirubin and for filter paper blood spots and recorded any side effects
Subsequently pregnant women were seen at the antenatal clinic monthly and for those with 32 weeks and above of gestation fortnightly At these visits they were actively screened for peripheral parasitaemia using OptiMAL dipstick test At any time before delivery if the test was negative the woman remained on daily haematinics If women who were already enrolled had positive antigen test confirmed by microscopy they received another course of the treatment they were initially assigned to Women were enrolled in the study only for the first episode of malaria detected during the antenatal visit At delivery midwives recorded birth weights and any stillbirths perinatal deaths or congenital abnormalities They also made slides from peripheral placental and cord blood and sampled maternal blood for haemoglobin measurements Any record of a congenital deformity was verified and confirmed by a clinician The women and their babies were visited at home at six weeks post delivery to record any neonatal adverse events such as deaths or severe morbidity
Outcome measures
Primary
1 Prevalence of parasitaemia on days 14 and 28 post treatment
Secondary
1 Incidence of adverse drug events within seven days following treatment
2 Proportions of pregnant women withdrawn from the study due to the occurrence of adverse drug events clinical and laboratory by day 7 following initiation of treatment
3 Change in maternal haemoglobin concentrations at days 14 and 28 following treatment
4 Prevalence of peripheral parasitaemia at delivery
5 Prevalence of placental parasitaemia at delivery
6 Proportions of abnormal biochemistry and white blood cell values on days 14 and 28 post treatment
7 Sensitivity specificity positive and negative predictive values likelihood ratios and the area under receiver operating characteristic ROC curve for the OptiMAL antigen test
8 Incidences of adverse pregnancy outcomes in the study group
9 Prevalence of postpartum parasitaemia
10 Prevalence of postpartum anaemia
Sample Size
This was based on the assumption of a 28-day parasitological clearance of 90 for AQ SP and the AQSP combination and 78 for chloroquine α 5 power 90 Allowing for a 15 loss to follow-up 225 pregnant women were recruited into each of the 4 treatment arms of the study giving a total study size of 900 pregnant women
Data and safety monitoring board
A data and safety monitoring board DSMB was constituted for the project The board was responsible for
Regular monitoring of the data and safety issues concerned with the study
Reviewing the PIs reports on serious adverse events and making recommendations on further progress of the study
Reviewing the statistical analysis plan prior to breaking the study drug codes
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