MalariaPhase 4NCT00167843
Reducing the Effects of Malaria in Children by Administering Repeated Preventive Doses
A Phase 4 study testing sulfadoxine-pyrimethamine in people with Malaria, run by Albert Schweitzer Hospital at 1 site in Gabon.
Trial summary
The general goal of the project is to assess the infectious status and immunity of mothers and children living in a malaria region. A major part of the study involves administering an effective antimalarial, sulfadoxine-pyrimethamine (Fansidar®), to children at the same timepoints as vaccinations, i.e. Read more about this study
- Who is it for?
- Ages Up to 5 monthsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- sulfadoxine-pyrimethamine
- How many people
- 1,189 participants
- Where
- 1 siteGabon
- Study dates
- Dec 2002to Mar 2007
- Phase
- Phase 4
- 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 Up to 5 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Informed consent
- Permanent residence in the study area
Who cannot join
- Allergy/hypersensitivity to sulfonamides or pyrimethamine
- Signs of severe hepatic or renal dysfunction not due to malaria
Trial locations and contacts
1 site in 1 country.
Gabon1 site
Medical Research Unit of the Albert Schweitzer Hospital
Lambaréné, Moyen-Ogooué Province, B.P. 118
About this study
Official title: A Longitudinal Study Assessing the Infectious Status and Immunity of Mothers and Their Children in Lambaréné, Including Intermittent Treatment of Children With Sulfadoxine-pyrimethamine for Malaria Control and Its Impact on Long-term Health
The general goal of the project is to assess the infectious status and immunity of mothers and children living in a malaria region. A major part of the study involves administering an effective antimalarial, sulfadoxine-pyrimethamine (Fansidar®), to children at the same timepoints as vaccinations, i.e. at age 3, 9 and 15 months. The main objective is to study safety, efficacy, and consequences of such a strategy in particular the ability to reduce the risk of anemia.
Read the detailed description
More than 1.5 million deaths of African children under 5 years of age are due to Plasmodium falciparum malaria. There is an urgent need for available and affordable strategies to control malaria morbidity in childhood.
Malaria control measures have been assessed for their potential to reduce intensity of infection in order to decrease the risk of malaria. It has been shown that malaria prevention using drugs is potentially capable to reduce malaria morbidity, school absenteeism, and all-cause mortality. However, prevention using drugs in the first years of life can also result in the loss or delay of acquired resistance which can lead to a rebound phenomenon (i.e. an increased risk of severe malaria after the therapy ended). In a recent study on intermittent treatment with Fansidar® at 2, 3, and 9 months of age, the number of malaria cases during the first 12 months of life was significantly reduced and no rebound effect was observed. This study has demonstrated that the intermittent administration of Fansidar® is safe and has beneficial effects for the children. However, the effectiveness decreased some months after discontinuing the drug. The promising effect of the intermittent administration of fansidar shown in this study needs to be confirmed in areas of different endemicity such as Lambaréné, Gabon. It is assumed that a more extended intermittent application of Fansidar® than performed in the above example would likely result in a longer period of protection from malaria, and the extended intermittent administration of Fansidar should not lead to rebound effects resulting in a higher occurrence of malaria.
The framework of this study offers a unique opportunity to study characteristics of infectious disease of importance in the Lambaréné area and the development of resistance against microbes at the maternofetal (mother/foetus) interface. Comparable studies will simultaneously take place in two associated study sites (Kumasi and Tamale) with different malaria endemicity in Ghana, West Africa.
Comparison: Comparison of malaria attacks in children with and without intermittent Fansidar® treatment with drug administration at months 3 and 9 (alongside with routine vaccinations delivered through child vaccination programme) and an additional administration at month 15.
- Conditions
- Malaria
- Being tested
- sulfadoxine-pyrimethamine
- Keywords
- Malaria, Anemia, Children, Gabon, Intermittent preventive treatment
- Medical subject headings
- Malaria, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sulfadoxine-pyrimethamineDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy:
The proportion of children with at least one episode of anemia from 3 to 18 months of life
The proportion of children with at least one episode of malaria from 3 to 18 months of life
Safety:
The proportion of children with at least one episode of an adverse event
The proportion of children with at least one episode of a serious adverse event
Rebound:
The proportion of children with at least one episode of anemia from 18-30 months of life, the proportion of children with at least one episode of malaria from 18-30 months of life
Secondary outcomes (10)
Proportion of children with at least one episode of severe anemia
Proportion of hospitalized children with anemia
Proportion of hospitalized children with malaria
Proportion of hospitalized children with any disease
Proportion of children with at least one episode of anemia from 3 to 12 months of life
Proportion of children with at least one episode of malaria from 3 to 12 months of life.
Parasite drug resistance after intermittent sulfadoxine-pyrimethamine and placebo application
Multiplicity of P. falciparum infections after the intermittent treatment
Antibody responses against variable parasite genes after the intermittent treatment
Specific responses to malaria vaccine candidates during the study period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2005 (estimated)
- Study startDec 2002
- Study completionMar 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 1,189 participants
Sponsor and investigators
- Lead sponsor
- Albert Schweitzer Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Unit, Lambarene, Bundesministerium fuer Bildung und Forschung (BMBF), Deutscher Akademischer Austausch Dienst, German Research Foundation, Bill and Melinda Gates Foundation
- Investigators
- Peter G Kremsner, MD, Principal investigator, Albert Schweitzer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00167843
- Sponsor's protocol ID
- 28574
- Status last verified
- Jan 2013
- First submitted
- 11 Sep 2005
- Last updated
- 24 Jan 2013
- Results posted
- No
Publications
WHO. In WHO report: Fostering Development, Geneva, 1996
Greenwood BM, Greenwood AM, Bradley AK, Snow RW, Byass P, Hayes RJ, N'Jie AB. Comparison of two strategies for control of malaria within a primary health care programme in the Gambia. Lancet. 1988 May 21;1(8595):1121-7. doi: 10.1016/s0140-6736(88)91949-6.
PubMed 2896957Menendez C, Kahigwa E, Hirt R, Vounatsou P, Aponte JJ, Font F, Acosta CJ, Schellenberg DM, Galindo CM, Kimario J, Urassa H, Brabin B, Smith TA, Kitua AY, Tanner M, Alonso PL. Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants. Lancet. 1997 Sep 20;350(9081):844-50. doi: 10.1016/S0140-6736(97)04229-3.
PubMed 9310602Schellenberg D, Menendez C, Kahigwa E, Aponte J, Vidal J, Tanner M, Mshinda H, Alonso P. Intermittent treatment for malaria and anaemia control at time of routine vaccinations in Tanzanian infants: a randomised, placebo-controlled trial. Lancet. 2001 May 12;357(9267):1471-7. doi: 10.1016/S0140-6736(00)04643-2.
PubMed 11377597Bradley-Moore AM, Greenwood BM, Bradley AK, Bartlett A, Bidwell DE, Voller A, Kirkwood BR, Gilles HM. Malaria chemoprophylaxis with chloroquine in young Nigerian children. I. Its effect on mortality, morbidity and the prevalence of malaria. Ann Trop Med Parasitol. 1985 Dec;79(6):549-62. doi: 10.1080/00034983.1985.11811962.
PubMed 3914860Diagne N, Rogier C, Sokhna CS, Tall A, Fontenille D, Roussilhon C, Spiegel A, Trape JF. Increased susceptibility to malaria during the early postpartum period. N Engl J Med. 2000 Aug 31;343(9):598-603. doi: 10.1056/NEJM200008313430901.
PubMed 10965006Gabor JJ, Schwarz NG, Esen M, Kremsner PG, Grobusch MP. Dengue and chikungunya seroprevalence in Gabonese infants prior to major outbreaks in 2007 and 2010: A sero-epidemiological study. Travel Med Infect Dis. 2016 Jan-Feb;14(1):26-31. doi: 10.1016/j.tmaid.2016.01.005. Epub 2016 Jan 29.
PubMed 26869532Grobusch MP, Gabor JJ, Aponte JJ, Schwarz NG, Poetschke M, Doernemann J, Schuster K, Koester KB, Profanter K, Borchert LB, Kurth F, Pongratz P, Issifou S, Lell B, Kremsner PG. No rebound of morbidity following intermittent preventive sulfadoxine-pyrimethamine treatment of malaria in infants in Gabon. J Infect Dis. 2009 Dec 1;200(11):1658-61. doi: 10.1086/647990.
PubMed 19848610May J, Adjei S, Busch W, Gabor JJ, Issifou S, Kobbe R, Kreuels B, Lell B, Schwarz NG, Adjei O, Kremsner PG, Grobusch MP. Therapeutic and prophylactic effect of intermittent preventive anti-malarial treatment in infants (IPTi) from Ghana and Gabon. Malar J. 2008 Oct 1;7:198. doi: 10.1186/1475-2875-7-198.
PubMed 18828899Grobusch MP, Lell B, Schwarz NG, Gabor J, Dornemann J, Potschke M, Oyakhirome S, Kiessling GC, Necek M, Langin MU, Klein Klouwenberg P, Klopfer A, Naumann B, Altun H, Agnandji ST, Goesch J, Decker M, Salazar CL, Supan C, Kombila DU, Borchert L, Koster KB, Pongratz P, Adegnika AA, Glasenapp Iv, Issifou S, Kremsner PG. Intermittent preventive treatment against malaria in infants in Gabon--a randomized, double-blind, placebo-controlled trial. J Infect Dis. 2007 Dec 1;196(11):1595-602. doi: 10.1086/522160. Epub 2007 Oct 25.
PubMed 18008242
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Longitudinal Study Assessing the Infectious Status and Immunity of Mothers and Their Children in Lambaréné, Including Intermittent Treatment of Children With Sulfadoxine-pyrimethamine for Malaria Control and Its Impact on Long-term Health
- ClinicalTrials.gov ID
- NCT00167843
- Acronym / sponsor ID
- 28574
- Conditions
- Malaria
- Keywords
- Malaria, Anemia, Children, Gabon, Intermittent preventive treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,189 participants
- Lead sponsor
- Albert Schweitzer HospitalUniversity, hospital or other
- Collaborators
- Medical Research Unit, Lambarene, Bundesministerium fuer Bildung und Forschung (BMBF), Deutscher Akademischer Austausch Dienst, German Research Foundation, Bill and Melinda Gates Foundation
- Study start
- Dec 2002
- Study completion
- Mar 2007
- First posted
- 14 Sep 2005 (estimated)
- 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.
The general goal of the project is to assess the infectious status and immunity of mothers and children living in a malaria region. A major part of the study involves administering an effective antimalarial, sulfadoxine-pyrimethamine (Fansidar®), to children at the same timepoints as vaccinations, i.e. at age 3, 9 and 15 months. The main objective is to study safety, efficacy, and consequences of such a strategy in particular the ability to reduce the risk of anemia.
Detailed description
More than 1.5 million deaths of African children under 5 years of age are due to Plasmodium falciparum malaria. There is an urgent need for available and affordable strategies to control malaria morbidity in childhood.
Malaria control measures have been assessed for their potential to reduce intensity of infection in order to decrease the risk of malaria. It has been shown that malaria prevention using drugs is potentially capable to reduce malaria morbidity, school absenteeism, and all-cause mortality. However, prevention using drugs in the first years of life can also result in the loss or delay of acquired resistance which can lead to a rebound phenomenon (i.e. an increased risk of severe malaria after the therapy ended). In a recent study on intermittent treatment with Fansidar® at 2, 3, and 9 months of age, the number of malaria cases during the first 12 months of life was significantly reduced and no rebound effect was observed. This study has demonstrated that the intermittent administration of Fansidar® is safe and has beneficial effects for the children. However, the effectiveness decreased some months after discontinuing the drug. The promising effect of the intermittent administration of fansidar shown in this study needs to be confirmed in areas of different endemicity such as Lambaréné, Gabon. It is assumed that a more extended intermittent application of Fansidar® than performed in the above example would likely result in a longer period of protection from malaria, and the extended intermittent administration of Fansidar should not lead to rebound effects resulting in a higher occurrence of malaria.
The framework of this study offers a unique opportunity to study characteristics of infectious disease of importance in the Lambaréné area and the development of resistance against microbes at the maternofetal (mother/foetus) interface. Comparable studies will simultaneously take place in two associated study sites (Kumasi and Tamale) with different malaria endemicity in Ghana, West Africa.
Comparison: Comparison of malaria attacks in children with and without intermittent Fansidar® treatment with drug administration at months 3 and 9 (alongside with routine vaccinations delivered through child vaccination programme) and an additional administration at month 15.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- Up to 5 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Informed consent
- Permanent residence in the study area
Key exclusion criteria (2 listed)
- Allergy/hypersensitivity to sulfonamides or pyrimethamine
- Signs of severe hepatic or renal dysfunction not due to malaria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sulfadoxine-pyrimethamine | Drug | – |
Primary outcome
Efficacy:
The proportion of children with at least one episode of anemia from 3 to 18 months of life
The proportion of children with at least one episode of malaria from 3 to 18 months of life
Safety:
The proportion of children with at least one episode of an adverse event
The proportion of children with at least one episode of a serious adverse event
Rebound:
The proportion of children with at least one episode of anemia from 18-30 months of life, the proportion of children with at least one episode of malaria from 18-30 months of life
10 secondary outcomes
Proportion of children with at least one episode of severe anemia
Proportion of hospitalized children with anemia
Proportion of hospitalized children with malaria
Proportion of hospitalized children with any disease
Proportion of children with at least one episode of anemia from 3 to 12 months of life
Proportion of children with at least one episode of malaria from 3 to 12 months of life.
Parasite drug resistance after intermittent sulfadoxine-pyrimethamine and placebo application
Multiplicity of P. falciparum infections after the intermittent treatment
Antibody responses against variable parasite genes after the intermittent treatment
Specific responses to malaria vaccine candidates during the study period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2013.
- BackgroundWHO. In WHO report: Fostering Development, Geneva, 1996
- Background: PubMed 2896957Greenwood BM, Greenwood AM, Bradley AK, Snow RW, Byass P, Hayes RJ, N'Jie AB. Comparison of two strategies for control of malaria within a primary health care programme in the Gambia. Lancet. 1988 May 21;1(8595):1121-7. doi: 10.1016/s0140-6736(88)91949-6.
- Background: PubMed 9310602Menendez C, Kahigwa E, Hirt R, Vounatsou P, Aponte JJ, Font F, Acosta CJ, Schellenberg DM, Galindo CM, Kimario J, Urassa H, Brabin B, Smith TA, Kitua AY, Tanner M, Alonso PL. Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants. Lancet. 1997 Sep 20;350(9081):844-50. doi: 10.1016/S0140-6736(97)04229-3.
- Background: PubMed 11377597Schellenberg D, Menendez C, Kahigwa E, Aponte J, Vidal J, Tanner M, Mshinda H, Alonso P. Intermittent treatment for malaria and anaemia control at time of routine vaccinations in Tanzanian infants: a randomised, placebo-controlled trial. Lancet. 2001 May 12;357(9267):1471-7. doi: 10.1016/S0140-6736(00)04643-2.
- Background: PubMed 3914860Bradley-Moore AM, Greenwood BM, Bradley AK, Bartlett A, Bidwell DE, Voller A, Kirkwood BR, Gilles HM. Malaria chemoprophylaxis with chloroquine in young Nigerian children. I. Its effect on mortality, morbidity and the prevalence of malaria. Ann Trop Med Parasitol. 1985 Dec;79(6):549-62. doi: 10.1080/00034983.1985.11811962.
- Background: PubMed 10965006Diagne N, Rogier C, Sokhna CS, Tall A, Fontenille D, Roussilhon C, Spiegel A, Trape JF. Increased susceptibility to malaria during the early postpartum period. N Engl J Med. 2000 Aug 31;343(9):598-603. doi: 10.1056/NEJM200008313430901.
- Derived from this study: PubMed 26869532Gabor JJ, Schwarz NG, Esen M, Kremsner PG, Grobusch MP. Dengue and chikungunya seroprevalence in Gabonese infants prior to major outbreaks in 2007 and 2010: A sero-epidemiological study. Travel Med Infect Dis. 2016 Jan-Feb;14(1):26-31. doi: 10.1016/j.tmaid.2016.01.005. Epub 2016 Jan 29.
- Derived from this study: PubMed 19848610Grobusch MP, Gabor JJ, Aponte JJ, Schwarz NG, Poetschke M, Doernemann J, Schuster K, Koester KB, Profanter K, Borchert LB, Kurth F, Pongratz P, Issifou S, Lell B, Kremsner PG. No rebound of morbidity following intermittent preventive sulfadoxine-pyrimethamine treatment of malaria in infants in Gabon. J Infect Dis. 2009 Dec 1;200(11):1658-61. doi: 10.1086/647990.
- Derived from this study: PubMed 18828899May J, Adjei S, Busch W, Gabor JJ, Issifou S, Kobbe R, Kreuels B, Lell B, Schwarz NG, Adjei O, Kremsner PG, Grobusch MP. Therapeutic and prophylactic effect of intermittent preventive anti-malarial treatment in infants (IPTi) from Ghana and Gabon. Malar J. 2008 Oct 1;7:198. doi: 10.1186/1475-2875-7-198.
- Derived from this study: PubMed 18008242Grobusch MP, Lell B, Schwarz NG, Gabor J, Dornemann J, Potschke M, Oyakhirome S, Kiessling GC, Necek M, Langin MU, Klein Klouwenberg P, Klopfer A, Naumann B, Altun H, Agnandji ST, Goesch J, Decker M, Salazar CL, Supan C, Kombila DU, Borchert L, Koster KB, Pongratz P, Adegnika AA, Glasenapp Iv, Issifou S, Kremsner PG. Intermittent preventive treatment against malaria in infants in Gabon--a randomized, double-blind, placebo-controlled trial. J Infect Dis. 2007 Dec 1;196(11):1595-602. doi: 10.1086/522160. Epub 2007 Oct 25.
- Homepage of IPTi consortiumLink provided by the sponsor.
- Homepage of the Medical Research Unit of the Albert Schweitzer HospitalLink provided by the sponsor.
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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.
Peter G Kremsner, MD principal investigator
Albert Schweitzer Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing sulfadoxine-pyrimethamine in people with Malaria, run by Albert Schweitzer Hospital at 1 site in Gabon.
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 2 inclusion and 2 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: finished, as of the sponsor's last update on 24 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Gabon. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy:. The study lists 8 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 NCT00167843, which also lists 10 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 24 Jan 2013.