Ignite Creation Date:
2024-05-06 @ 1:09 AM
Last Modification Date:
2024-10-26 @ 11:00 AM
Study NCT ID:
NCT01746199
Status:
COMPLETED
Last Update Posted:
2020-11-30
First Post:
2012-11-30
Brief Title:
Efficacy of Antifolates Against Malaria in HIV-infected Pregnant Women and the Emergence of Induced Resistance in Plasmodium Falciparum
Sponsor:
Institut Pasteur
Organization:
Institut Pasteur
Study Overview
Official Title:
Comparative Study of Efficacy of Two Antifolates Prophylactic Strategies Against Malaria in HIV Positive Pregnant Women MACOMBA Study
Status:
COMPLETED
Status Verified Date:
2020-11
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:
MACOMBA
Brief Summary:
Given the resistance emergence of malaria in pregnant women receiving intermittent preventive treatment with sulfadoxine-pyrimethamine IPT-SP and the burden of this infection among pregnant women infected by HIV it is urgent to seek a more effective alternative treatment to optimize the prevention of malaria Cotrimoxazole CTM actually administered daily as a prophylactic mean to opportunistic infections for HIV infected patients showed encouraging results in preventing malaria in pregnant women However these results must be confirmed by randomized trials particularly in pregnant women
The main objective of this clinical trial is to compare the efficacy of cotrimoxazole CTM administered once daily with IPT-SP 3 curative doses spaced one month on placental parasitaemia in pregnant women infected with HIV and cluster of differentiation 4 CD4 350 cellsmm3
The main hypothesis is based on the premise that cotrimoxazole is more effective than IPT-SP for placental parasitaemia This might be due to the higher plasma concentration of cotrimoxazole attained with daily doses If this hypothesis is proven cotrimoxazole could be recommended as prophylaxis for HIV-positive pregnant women whatever their CD4 cell count In this study the investigators will also test the hypothesis that the strains of Plasmodium falciparum isolated from HIV-positive pregnant women express more dhfr and dhps resistance markers
The main objective of this clinical trial is to compare the efficacy of cotrimoxazole CTM administered once daily with IPT-SP 3 curative doses spaced one month on placental parasitaemia in pregnant women infected with HIV and cluster of differentiation 4 CD4 350 cellsmm3
The main hypothesis is based on the premise that cotrimoxazole is more effective than IPT-SP for placental parasitaemia This might be due to the higher plasma concentration of cotrimoxazole attained with daily doses If this hypothesis is proven cotrimoxazole could be recommended as prophylaxis for HIV-positive pregnant women whatever their CD4 cell count In this study the investigators will also test the hypothesis that the strains of Plasmodium falciparum isolated from HIV-positive pregnant women express more dhfr and dhps resistance markers
Detailed Description:
Ascertainment of HIV serological status has become a prerequisite for better prevention of malaria Studies reported that cotrimoxazole reduces malaria episodes in adults other than pregnant women and in children Furthermore several studies showed a good clinical and parasitological response to cotrimoxazole in treated children Therefore preventive treatment with SP for all HIV patients including pregnant women who are receiving treatment containing cotrimoxazole is superfluous and is even contraindicated because of the increase risk of severe adverse reactions Few studies however have described the efficacy of cotrimoxazole in the prevention of malaria in pregnant women particularly in an area where the frequency of therapeutic failures with SP in cases of Plasmodium falciparum malaria is increasing
The emergence and augmentation of the frequency of resistance of Plasmodium falciparum to SP which has already been observed in numerous countries of sub-Saharan Africa and in the Central African Republic challenges the short-term usefulness of this drug combination in the prevention of malaria in pregnant women The resistance is due to accumulation of point mutations at various sites on the genes coding for dihydrofolate reductase dhfr and dihydropteroate synthase dhps The number of mutations correlates with the extent of resistance of Plasmodium falciparum to SP in vitro In studies carried out in Bangui the prevalence of therapeutic failure was estimated to be 238 after 14 days of follow-up among children with uncomplicated malaria while the resistance of Plasmodium falciparum to pyrimethamine in vitro was reported to be 383 The frequency of mutations in dhfr and dhps alleles is correlated with in vitro response of Plasmodium falciparum strains to SP
Pregnancy and HIV infection increase the risk for emergence of mutated strains that are resistant to SP because a wide variety of types and clones are found in parasitaemia in pregnant women genetic diversity Furthermore some studies raised concern about the possible development of cross-resistance of Plasmodium falciparum to both cotrimoxazole and SP because of the similarity of their mode of action although this hypothesis has not been proven
The national malaria programme in the Central African Republic recommends the use of IPT-SP since 2006
The investigators main hypothesis is based on the premise that cotrimoxazole is more effective than SP for placental parasitaemia This might be due to the higher plasma concentration of cotrimoxazole attained with daily doses If this hypothesis is proven cotrimoxazole could be recommended as prophylaxis for HIV pregnant women whatever their CD4 cell count In this study the investigators will also test the hypothesis that the strains of Plasmodium falciparum isolated from HIV positive pregnant women express more dhfr and dhps resistance markers
The emergence and augmentation of the frequency of resistance of Plasmodium falciparum to SP which has already been observed in numerous countries of sub-Saharan Africa and in the Central African Republic challenges the short-term usefulness of this drug combination in the prevention of malaria in pregnant women The resistance is due to accumulation of point mutations at various sites on the genes coding for dihydrofolate reductase dhfr and dihydropteroate synthase dhps The number of mutations correlates with the extent of resistance of Plasmodium falciparum to SP in vitro In studies carried out in Bangui the prevalence of therapeutic failure was estimated to be 238 after 14 days of follow-up among children with uncomplicated malaria while the resistance of Plasmodium falciparum to pyrimethamine in vitro was reported to be 383 The frequency of mutations in dhfr and dhps alleles is correlated with in vitro response of Plasmodium falciparum strains to SP
Pregnancy and HIV infection increase the risk for emergence of mutated strains that are resistant to SP because a wide variety of types and clones are found in parasitaemia in pregnant women genetic diversity Furthermore some studies raised concern about the possible development of cross-resistance of Plasmodium falciparum to both cotrimoxazole and SP because of the similarity of their mode of action although this hypothesis has not been proven
The national malaria programme in the Central African Republic recommends the use of IPT-SP since 2006
The investigators main hypothesis is based on the premise that cotrimoxazole is more effective than SP for placental parasitaemia This might be due to the higher plasma concentration of cotrimoxazole attained with daily doses If this hypothesis is proven cotrimoxazole could be recommended as prophylaxis for HIV pregnant women whatever their CD4 cell count In this study the investigators will also test the hypothesis that the strains of Plasmodium falciparum isolated from HIV positive pregnant women express more dhfr and dhps resistance markers
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