Pregnancy MalariaDEEM-FITNCT04634695
Assessing to What Extent Dhps-431V Mutation May Influence the Protective Efficacy of IPTp-SP
An observational study of Pregnancy Malaria, run by Obafemi Awolowo University at 2 sites in Nigeria.
Trial summary
Malaria in pregnancy (MiP) continues to be a significant public health issue, particularly in sub-Saharan Africa. The coverage of pregnant women with three or more doses of intermittent preventive treatment using sulphadoxine-pyrimethamine (IPTp-SP) is recommended to prevent risks associated with MiP in… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Pregnancy Malaria
- How many people
- 288 participants
- Where
- 2 sitesNigeria
- Study dates
- 10 Aug 2020to 1 Jul 2021
- How long will I take part?
- 3 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Study population: Antenatal care (ANC) contact schedule with proposed timelines for implementation of malaria in pregnancy interventions designed by WHO(16) will be followed in recruiting subjects from 26 weeks of pregnancy. The study will be conducted at the antenatal clinics of Obafemi Awolowo University Teaching Hospitals complex, Ile-Ife
Who may be able to join
- Pregnant women at 26 weeks of pregnancy who aged ≥ 18 years; Must have commenced IPTp-SP and intended to receive three or more therapeutic doses of SP before delivery; Readiness to give informed consent and comply with the study protocol.
Who cannot join
- Pregnant women during their first trimester as SP is not recommended during the first trimester; Severe or complicated malaria as the subject will require additional treatment and consideration; Presence of underlying chronic or severe diseases (e.g., cardiac, renal or hepatic diseases, HIV/AIDS); Individuals who are receiving co-trimoxazole for another disease condition (as SP is not usually recommended): Inability to swallow oral medication because of persistent nausea and vomiting
Trial locations and contacts
2 sites in 1 country.
Nigeria2 sites, 2 recruiting
- Recruiting
Obafemi Awolowo University Teaching Hospital
Ile-Ife, Osun State, +234
Adebanjo Adegbola, PhD, +2348035816301, banjogbola@yahoo.com
Adebimpe O Ijarotimi, FMCOG, +2348034002812, tadeolar@yahoo.com
- Recruiting
State Specialist Hospital, Asubiaro
Osogbo, Osun State, +234
Adebanjo Adegbola, PhD, +2348035816301, banjogbola@yahoo.com
Dr Babalola E O, FMCOG, 07065266822
About this study
Official title: Assessing the Prevalence and Impact of Dihydropteroate Synthase-431V Mutation on the Protective Efficacy of Intermittent Preventive Treatment During Pregnancy Using Sulphadoxine-pyrimethamine
Malaria in pregnancy (MiP) continues to be a significant public health issue, particularly in sub-Saharan Africa. The coverage of pregnant women with three or more doses of intermittent preventive treatment using sulphadoxine-pyrimethamine (IPTp-SP) is recommended to prevent risks associated with MiP in moderate-to-high transmission settings. Evidence has recently become available supporting the emergence of a novel Pfdhps-431V mutation in Nigeria. This new mutation may further confound the existing SP-resistance; thus, the intended follow-on project aims to assess the influence of Pfdhps-431V mutation on the protective efficacy of SP during pregnancy.
The aims are to detect P. falciparum positivity at delivery and pregnancy outcome in participants who must have received three or more doses of IPTp_SP. We will attempt to check the presence of existing and new Pfdhps/Pfdhfr mutations in the samples positive for P. falciparum using a quantitative PCR (qPCR). The prevalence of novel Pfdhps-431V mutant and other Pfdhps/Pfdhfr resistance alleles among the study population will be estimated. The significance of the resistance genes on the efficacy of SP will be described by looking at its associations with the reported IPTp use, P. falciparum infection, maternal anaemia, low birth weight, and preterm delivery.
Read the detailed description
Malaria in pregnancy (MiP) is considered a major public health issue with substantial risks for mothers and their babies. Intermittent preventive treatment in pregnancy using sulphadoxine-pyrimethamine (IPTp-SP) is adopted as a part of antenatal care (ANC) to prevent malaria and reduce the risk associated with MiP. However, SP-resistance is increasing with the emergence of Plasmodium falciparum dihydropteroate synthase (Pfdhps) and P. falciparum dihydrofolate reductase (Pfdhfr) resistant genes challenging the benefits and effectiveness of IPTp-SP. Still, evidence has become available supporting the emergence of a novel Pfdhps-I431V mutation. The I431V mutation is found only in West and Central African countries, however, its impact on SP resistance has not been evaluated. We are hypothesizing that the new mutation may confound the existing SP-resistance resulting in an apparent reduction in the protective effect of SP during pregnancy within the region.
The study will recruit adult pregnant women and will assess the presence of malaria infection at delivery. The study will seek new mutations in vivo using full sequencing. This molecular tool will also be used to look at the prevalence of novel Pfdhps-431V mutation among pregnant women undergoing monthly IPTp-SP. Attempts will be made to re-evaluate the prevalence of other Pfdhps and Pfdhfr resistance alleles among the study population. The significance of the resistance genes on the protective efficacy of SP will be described.
The present study is an observational study to be conducted among all booked pregnant women. The pregnant women must have received at least three therapeutic doses of sulphadoxine-pyrimethamine as part of routine antenatal care (ANC) before delivery. sion and Pregnant women who consented to participate will be tested for the presence of malaria parasite during the third trimester and at delivery. 80-100 µL blood samples will be saved as dried blood spot on Whatman® filter paper from the individual with P. falciparum malaria positivity Antenatal care (ANC) contact schedule with proposed timelines for implementation of malaria in pregnancy interventions designed by WHO will be followed in enrolling subjects from 26 weeks of pregnancy. The study will be conducted at the antenatal
- Conditions
- Pregnancy Malaria
- Keywords
- Antimalarial drug, Sulphadoxine-pyrimethamine, SP-resistance, Malaria in Pregnancy, mutation, Intermittent Preventive treatment
What is being measured
The primary outcome is the main question the study is designed to answer.
Malaria infection at the time of delivery
- falciparum malaria positivity will be confirmed using microscopy
Measured: May 2021
Dhps-431V mutation
Point mutation at codon dhps-I431V will be carried out
Measured: May 2021
Secondary outcomes (3)
Average maternal haematocrit
Maternal haematocrit will be carried out to confirm whether the mother is anaemic or not
Measured: May 2021
Birth weight of babies
Birth weight of babies
Measured: May 2021
Prevalence of placental malaria
Prevalence of placental malaria
Measured: May 2021
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2020
- Study start10 Aug 2020
- Primary completion31 May 2021 (estimated)
- Study completion1 Jul 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Pregnancy MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 288 participants (estimated)
- Target duration
- 3 Months
Sponsor and investigators
- Lead sponsor
- Obafemi Awolowo University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Copenhagen, London School of Hygiene and Tropical Medicine, European and Developing Countries Clinical Trials Partnership (EDCTP)
- Responsible party
- Sponsor
- Investigators
- Adebanjo Adegbola, PhD, Principal investigator, Obafemi Awolowo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04634695
- Sponsor's protocol ID
- DEEM-FIT
- Acronym
- DEEM-FIT
- Status last verified
- Nov 2020
- First submitted
- 2 Nov 2020
- Last updated
- 18 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
van Eijk AM, Larsen DA, Kayentao K, Koshy G, Slaughter DEC, Roper C, Okell LC, Desai M, Gutman J, Khairallah C, Rogerson SJ, Hopkins Sibley C, Meshnick SR, Taylor SM, Ter Kuile FO. Effect of Plasmodium falciparum sulfadoxine-pyrimethamine resistance on the effectiveness of intermittent preventive therapy for malaria in pregnancy in Africa: a systematic review and meta-analysis. Lancet Infect Dis. 2019 May;19(5):546-556. doi: 10.1016/S1473-3099(18)30732-1. Epub 2019 Mar 25.
PubMed 30922818Oguike MC, Falade CO, Shu E, Enato IG, Watila I, Baba ES, Bruce J, Webster J, Hamade P, Meek S, Chandramohan D, Sutherland CJ, Warhurst D, Roper C. Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V. Int J Parasitol Drugs Drug Resist. 2016 Dec;6(3):220-229. doi: 10.1016/j.ijpddr.2016.08.004. Epub 2016 Sep 29.
PubMed 27821281Alifrangis M, Nag S, Schousboe ML, Ishengoma D, Lusingu J, Pota H, Kavishe RA, Pearce R, Ord R, Lynch C, Dejene S, Cox J, Rwakimari J, Minja DT, Lemnge MM, Roper C. Independent origin of plasmodium falciparum antifolate super-resistance, Uganda, Tanzania, and Ethiopia. Emerg Infect Dis. 2014 Aug;20(8):1280-6. doi: 10.3201/eid2008.131897.
PubMed 25061906
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing the Prevalence and Impact of Dihydropteroate Synthase-431V Mutation on the Protective Efficacy of Intermittent Preventive Treatment During Pregnancy Using Sulphadoxine-pyrimethamine
- ClinicalTrials.gov ID
- NCT04634695
- Acronym / sponsor ID
- DEEM-FIT / DEEM-FIT
- Conditions
- Pregnancy Malaria
- Keywords
- Antimalarial drug, Sulphadoxine-pyrimethamine, SP-resistance, Malaria in Pregnancy, mutation, Intermittent Preventive treatment
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 288 participants (estimated)
- Lead sponsor
- Obafemi Awolowo UniversityUniversity, hospital or other
- Collaborators
- University of Copenhagen, London School of Hygiene and Tropical Medicine, European and Developing Countries Clinical Trials Partnership (EDCTP)
- Study start
- 10 Aug 2020 (actual)
- Primary completion
- 31 May 2021 (estimated)
- Study completion
- 1 Jul 2021 (estimated)
- First posted
- 18 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Malaria in pregnancy (MiP) continues to be a significant public health issue, particularly in sub-Saharan Africa. The coverage of pregnant women with three or more doses of intermittent preventive treatment using sulphadoxine-pyrimethamine (IPTp-SP) is recommended to prevent risks associated with MiP in moderate-to-high transmission settings. Evidence has recently become available supporting the emergence of a novel Pfdhps-431V mutation in Nigeria. This new mutation may further confound the existing SP-resistance; thus, the intended follow-on project aims to assess the influence of Pfdhps-431V mutation on the protective efficacy of SP during pregnancy.
The aims are to detect P. falciparum positivity at delivery and pregnancy outcome in participants who must have received three or more doses of IPTp_SP. We will attempt to check the presence of existing and new Pfdhps/Pfdhfr mutations in the samples positive for P. falciparum using a quantitative PCR (qPCR). The prevalence of novel Pfdhps-431V mutant and other Pfdhps/Pfdhfr resistance alleles among the study population will be estimated. The significance of the resistance genes on the efficacy of SP will be described by looking at its associations with the reported IPTp use, P. falciparum infection, maternal anaemia, low birth weight, and preterm delivery.
Detailed description
Malaria in pregnancy (MiP) is considered a major public health issue with substantial risks for mothers and their babies. Intermittent preventive treatment in pregnancy using sulphadoxine-pyrimethamine (IPTp-SP) is adopted as a part of antenatal care (ANC) to prevent malaria and reduce the risk associated with MiP. However, SP-resistance is increasing with the emergence of Plasmodium falciparum dihydropteroate synthase (Pfdhps) and P. falciparum dihydrofolate reductase (Pfdhfr) resistant genes challenging the benefits and effectiveness of IPTp-SP. Still, evidence has become available supporting the emergence of a novel Pfdhps-I431V mutation. The I431V mutation is found only in West and Central African countries, however, its impact on SP resistance has not been evaluated. We are hypothesizing that the new mutation may confound the existing SP-resistance resulting in an apparent reduction in the protective effect of SP during pregnancy within the region.
The study will recruit adult pregnant women and will assess the presence of malaria infection at delivery. The study will seek new mutations in vivo using full sequencing. This molecular tool will also be used to look at the prevalence of novel Pfdhps-431V mutation among pregnant women undergoing monthly IPTp-SP. Attempts will be made to re-evaluate the prevalence of other Pfdhps and Pfdhfr resistance alleles among the study population. The significance of the resistance genes on the protective efficacy of SP will be described.
The present study is an observational study to be conducted among all booked pregnant women. The pregnant women must have received at least three therapeutic doses of sulphadoxine-pyrimethamine as part of routine antenatal care (ANC) before delivery. sion and Pregnant women who consented to participate will be tested for the presence of malaria parasite during the third trimester and at delivery. 80-100 µL blood samples will be saved as dried blood spot on Whatman® filter paper from the individual with P. falciparum malaria positivity Antenatal care (ANC) contact schedule with proposed timelines for implementation of malaria in pregnancy interventions designed by WHO will be followed in enrolling subjects from 26 weeks of pregnancy. The study will be conducted at the antenatal
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Target follow-up
- 3 Months
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Antenatal care (ANC) contact schedule with proposed timelines for implementation of malaria in pregnancy interventions designed by WHO(16) will be followed in recruiting subjects from 26 weeks of pregnancy. The study will be conducted at the antenatal clinics of Obafemi Awolowo University Teaching Hospitals complex, Ile-Ife
Key inclusion criteria (1 listed)
- Pregnant women at 26 weeks of pregnancy who aged ≥ 18 years; Must have commenced IPTp-SP and intended to receive three or more therapeutic doses of SP before delivery; Readiness to give informed consent and comply with the study protocol.
Key exclusion criteria (1 listed)
- Pregnant women during their first trimester as SP is not recommended during the first trimester; Severe or complicated malaria as the subject will require additional treatment and consideration; Presence of underlying chronic or severe diseases (e.g., cardiac, renal or hepatic diseases, HIV/AIDS); Individuals who are receiving co-trimoxazole for another disease condition (as SP is not usually recommended): Inability to swallow oral medication because of persistent nausea and vomiting
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Malaria infection at the time of delivery
Time frame: May 2021
P. falciparum malaria positivity will be confirmed using microscopy
Dhps-431V mutation
Time frame: May 2021
Point mutation at codon dhps-I431V will be carried out
3 secondary outcomes
Average maternal haematocrit
Time frame: May 2021
Birth weight of babies
Time frame: May 2021
Prevalence of placental malaria
Time frame: May 2021
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2020.
- Background: PubMed 30922818van Eijk AM, Larsen DA, Kayentao K, Koshy G, Slaughter DEC, Roper C, Okell LC, Desai M, Gutman J, Khairallah C, Rogerson SJ, Hopkins Sibley C, Meshnick SR, Taylor SM, Ter Kuile FO. Effect of Plasmodium falciparum sulfadoxine-pyrimethamine resistance on the effectiveness of intermittent preventive therapy for malaria in pregnancy in Africa: a systematic review and meta-analysis. Lancet Infect Dis. 2019 May;19(5):546-556. doi: 10.1016/S1473-3099(18)30732-1. Epub 2019 Mar 25.
- Results publication: PubMed 27821281Oguike MC, Falade CO, Shu E, Enato IG, Watila I, Baba ES, Bruce J, Webster J, Hamade P, Meek S, Chandramohan D, Sutherland CJ, Warhurst D, Roper C. Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V. Int J Parasitol Drugs Drug Resist. 2016 Dec;6(3):220-229. doi: 10.1016/j.ijpddr.2016.08.004. Epub 2016 Sep 29.
- Results publication: PubMed 25061906Alifrangis M, Nag S, Schousboe ML, Ishengoma D, Lusingu J, Pota H, Kavishe RA, Pearce R, Ord R, Lynch C, Dejene S, Cox J, Rwakimari J, Minja DT, Lemnge MM, Roper C. Independent origin of plasmodium falciparum antifolate super-resistance, Uganda, Tanzania, and Ethiopia. Emerg Infect Dis. 2014 Aug;20(8):1280-6. doi: 10.3201/eid2008.131897.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adebanjo Adegbola, PhD principal investigator
Obafemi Awolowo University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pregnancy Malaria, run by Obafemi Awolowo University at 2 sites in Nigeria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Nigeria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Adebanjo J Adegbola, PhD (+2348035816301, banjogbola@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Malaria infection at the time of delivery (time frame: May 2021). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04634695, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2020.