MalariaPhase 1/2NCT01319448
Intermittent Preventive Treatment for Malaria in Patient With Sickle Cell Disease
A Phase 1/2 study testing Proguanil, mefloquine plus artesunate and Sulfadoxine-pyrimethamine plus amodiaquine in people with Malaria and Sickle Cell Crisis, run by London School of Hygiene and Tropical Medicine at 1 site in Nigeria.
Trial summary
Malaria prophylaxis is recommended for sickle cell disease patients. In Nigeria, daily proguanil or weekly pyrimethamine are the most commonly prescribed regimens, but the current policy is not effective due to poor compliance and drug resistance. Read more about this study
- Who is it for?
- Ages 6 months to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria, Sickle Cell Crisis
- What is being tested?
- Proguanil, mefloquine plus artesunate and Sulfadoxine-pyrimethamine plus amodiaquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 270 participants
- Where
- 1 siteNigeria
- Study dates
- Sep 2011to Apr 2013
- Phase
- Phase 1/2
- 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 6 months to 45 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Age 6months or older and >=5kg
- Sickle cell clinic attendant
- Both males and females
- Agree to abide by the study protocol
- Give informed consent and assent
- Not acutely sick at the time of recruitment
- Not having additional chronic disease
- Hb genotype of SS and SC confirmed by electrophoresis
Who cannot join
- known allergy to any of the antimalarial drugs use in the trial,
- severe illnesses requiring urgent admission,
- treatment with sulfadoxine-pyrimethamine or mefloquine in the previous 2wks
- patients on cotrimoxazole prophylaxis
Trial locations and contacts
1 site in 1 country.
Nigeria1 site
Department of Paediatrics and Child Health, University of Ilorin Teaching Hospital
Ilorin, Kwara State
About this study
Official title: Safety and Tolerability of Bi-monthly Intermittent Preventive Treatment With Mefloquine-Artesunate or Sulfadoxine-Pyrimethamine Plus Amodiaquine for Prevention of Malaria and Related Complications in Patients With Sickle Cell Anaemia.
Malaria prophylaxis is recommended for sickle cell disease patients. In Nigeria, daily proguanil or weekly pyrimethamine are the most commonly prescribed regimens, but the current policy is not effective due to poor compliance and drug resistance. Intermittent treatment with a long acting drug regimen administered under supervision at clinic visits may be more effective. The aim of this trial is to compare the tolerability and acceptability of supervised bimonthly treatment with either sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ) or mefloquine plus artesunate (MQ+AS), with the daily proguanil. Two hundred and seventy patients with sickle cell disease attending the paediatric sickle cell disease clinic in Ilorin hospital who meet the eligibility criteria and have parental consent, will be randomized to one of three prophylactic regimens: daily proguanil, bimonthly sulfadoxine-pyrimethamine plus amodiaquine, or bimonthly mefloquine plus artesunate. Patients will be asked to return to clinic every two months and whenever they are sick. At enrollment, the study paediatrician will conduct a physical examination of the child, and collect a venous blood sample for a complete blood cell count and biochemical screen, determination of G6PD genotype, preparation of blood smears for malaria microscopy and a blood spot for determination of molecular markers of resistance. Four days after each clinic visit, patients will be interviewed (by phone and, for a subset, at home or in the clinic) to ask about compliance and adverse events. Participants will be followed for one year. The parents or carer will be encouraged to bring their child to the Outpatient Department clinic if the child becomes unwell. The primary outcome of the trial is tolerability, secondary outcomes are adherence to the regimen, and incidence of malaria and the number of hospitalizations over 12 months. If the bimonthly regimens are well tolerated and the preliminary data from this study are promising, a larger multicentre trial will be required to determine efficacy.
- Conditions
- Malaria, Sickle Cell Crisis
- Being tested
- Proguanil, mefloquine plus artesunate, Sulfadoxine-pyrimethamine plus amodiaquine
- Keywords
- Sickle cell disease, Malaria, Intermittent Preventive Treatment (IPT), prophylaxis
- Medical subject headings
- Malaria, Vaso-Occlusive Crises, Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProguanilDrug
Proguanil tablets, 1.5mg/kg/day
mefloquine plus artesunateDrug
This treatment is given once a day for 3 days. Patients weighing 5-8 kg receive one paediatric tablet per day, those weighing 9-17 kg two paediatric tablets, those weighing 18-29 kg one adult tablet and those weighing 30 kg and two adult tablets.
Sulfadoxine-pyrimethamine plus amodiaquineDrug
amodiaquine plus sulfadoxine-pyrimethamine supervised at each bimonthly clinic visit (amodiaquine 10mg/kg per day for three days and sulfadoxine-pyrimethamine (25/1.25 mg/kg) on the first day).
| Study group | Role | What they receive |
|---|---|---|
| Daily proguanil | Active comparator | Standard policy of a supply of proguanil tablets to be taken daily Receives: Drug: Proguanil |
| IPT with MQ+AS bimonthly | Experimental | Intermittent Preventive Treatment (IPT) consisting of a bimonthly course of treatment with mefloquine-artesunate (MQ+AS) Receives: Drug: mefloquine plus artesunate |
| IPT with SP+AQ bimonthly | Experimental | IPT with bimonthly course of treatment with sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ) Receives: Drug: Sulfadoxine-pyrimethamine plus amodiaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Measured: 12 months
Adherence to the recommended regimen
Measured: 12 months
Secondary outcomes (1)
Efficacy against malaria
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2011 (estimated)
- Study startSep 2011
- Primary completionApr 2013
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 270 participants (actual)
Sponsor and investigators
- Lead sponsor
- London School of Hygiene and Tropical Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council Unit, The Gambia, Wellcome Trust, University of Ilorin Teaching Hospital
- Responsible party
- Sponsor
- Investigators
- Paul J Milligan, PhD, Study chair, London School of Hygiene and Tropical MedicineKalifa Bojang, PhD, Study director, MRC LaboratoriesRasaq Olaosebikan, MD, Principal investigator, University of Ilorin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01319448
- Sponsor's protocol ID
- 5856
- Status last verified
- Mar 2014
- First submitted
- 16 Mar 2011
- Last updated
- 21 Mar 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Olaosebikan R, Ernest K, Bojang K, Mokuolu O, Rehman AM, Affara M, Nwakanma D, Kiechel JR, Ogunkunle T, Olagunju T, Murtala R, Omefe P, Lambe T, Bello S, Ibrahim O, Olorunsola B, Ojuawo A, Greenwood B, Milligan P. A Randomized Trial to Compare the Safety, Tolerability, and Effectiveness of 3 Antimalarial Regimens for the Prevention of Malaria in Nigerian Patients With Sickle Cell Disease. J Infect Dis. 2015 Aug 15;212(4):617-25. doi: 10.1093/infdis/jiv093. Epub 2015 Feb 20.
PubMed 25701866
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Tolerability of Bi-monthly Intermittent Preventive Treatment With Mefloquine-Artesunate or Sulfadoxine-Pyrimethamine Plus Amodiaquine for Prevention of Malaria and Related Complications in Patients With Sickle Cell Anaemia.
- ClinicalTrials.gov ID
- NCT01319448
- Acronym / sponsor ID
- 5856
- Conditions
- Malaria, Sickle Cell Crisis
- Keywords
- Sickle cell disease, Malaria, Intermittent Preventive Treatment (IPT), prophylaxis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 270 participants (actual)
- Lead sponsor
- London School of Hygiene and Tropical MedicineUniversity, hospital or other
- Collaborators
- Medical Research Council Unit, The Gambia, Wellcome Trust, University of Ilorin Teaching Hospital
- Study start
- Sep 2011
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 21 Mar 2011 (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.
Malaria prophylaxis is recommended for sickle cell disease patients. In Nigeria, daily proguanil or weekly pyrimethamine are the most commonly prescribed regimens, but the current policy is not effective due to poor compliance and drug resistance. Intermittent treatment with a long acting drug regimen administered under supervision at clinic visits may be more effective. The aim of this trial is to compare the tolerability and acceptability of supervised bimonthly treatment with either sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ) or mefloquine plus artesunate (MQ+AS), with the daily proguanil. Two hundred and seventy patients with sickle cell disease attending the paediatric sickle cell disease clinic in Ilorin hospital who meet the eligibility criteria and have parental consent, will be randomized to one of three prophylactic regimens: daily proguanil, bimonthly sulfadoxine-pyrimethamine plus amodiaquine, or bimonthly mefloquine plus artesunate. Patients will be asked to return to clinic every two months and whenever they are sick. At enrollment, the study paediatrician will conduct a physical examination of the child, and collect a venous blood sample for a complete blood cell count and biochemical screen, determination of G6PD genotype, preparation of blood smears for malaria microscopy and a blood spot for determination of molecular markers of resistance. Four days after each clinic visit, patients will be interviewed (by phone and, for a subset, at home or in the clinic) to ask about compliance and adverse events. Participants will be followed for one year. The parents or carer will be encouraged to bring their child to the Outpatient Department clinic if the child becomes unwell. The primary outcome of the trial is tolerability, secondary outcomes are adherence to the regimen, and incidence of malaria and the number of hospitalizations over 12 months. If the bimonthly regimens are well tolerated and the preliminary data from this study are promising, a larger multicentre trial will be required to determine efficacy.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Daily proguanil | Active comparator | Drug: ProguanilStandard policy of a supply of proguanil tablets to be taken daily |
| IPT with MQ+AS bimonthly | Experimental | Drug: mefloquine plus artesunateIntermittent Preventive Treatment (IPT) consisting of a bimonthly course of treatment with mefloquine-artesunate (MQ+AS) |
| IPT with SP+AQ bimonthly | Experimental | Drug: Sulfadoxine-pyrimethamine plus amodiaquineIPT with bimonthly course of treatment with sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ) |
Who may qualify
- Ages
- 6 months to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Age 6months or older and >=5kg
- Sickle cell clinic attendant
- Both males and females
- Agree to abide by the study protocol
- Give informed consent and assent
Key exclusion criteria (4 listed)
- known allergy to any of the antimalarial drugs use in the trial,
- severe illnesses requiring urgent admission,
- treatment with sulfadoxine-pyrimethamine or mefloquine in the previous 2wks
- patients on cotrimoxazole prophylaxis
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 |
|---|---|---|
| ProguanilProguanil tablets, 1.5mg/kg/day | Drug | Daily proguanil |
| mefloquine plus artesunateThis treatment is given once a day for 3 days. Patients weighing 5-8 kg receive one paediatric tablet per day, those weighing 9-17 kg two paediatric tablets, those weighing 18-29 kg one adult tablet and those weighing 30 kg and two adult tablets. | Drug | IPT with MQ+AS bimonthly |
| Sulfadoxine-pyrimethamine plus amodiaquineamodiaquine plus sulfadoxine-pyrimethamine supervised at each bimonthly clinic visit (amodiaquine 10mg/kg per day for three days and sulfadoxine-pyrimethamine (25/1.25 mg/kg) on the first day). | Drug | IPT with SP+AQ bimonthly |
Primary outcome
Incidence of adverse events
Time frame: 12 months
Adherence to the recommended regimen
Time frame: 12 months
1 secondary outcome
Efficacy against malaria
Time frame: 12 months
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 21 Mar 2014.
- Derived from this study: PubMed 25701866Olaosebikan R, Ernest K, Bojang K, Mokuolu O, Rehman AM, Affara M, Nwakanma D, Kiechel JR, Ogunkunle T, Olagunju T, Murtala R, Omefe P, Lambe T, Bello S, Ibrahim O, Olorunsola B, Ojuawo A, Greenwood B, Milligan P. A Randomized Trial to Compare the Safety, Tolerability, and Effectiveness of 3 Antimalarial Regimens for the Prevention of Malaria in Nigerian Patients With Sickle Cell Disease. J Infect Dis. 2015 Aug 15;212(4):617-25. doi: 10.1093/infdis/jiv093. Epub 2015 Feb 20.
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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.
Paul J Milligan, PhD study chair
London School of Hygiene and Tropical Medicine
Kalifa Bojang, PhD study director
MRC Laboratories
Rasaq Olaosebikan, MD principal investigator
University of Ilorin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Proguanil, mefloquine plus artesunate and Sulfadoxine-pyrimethamine plus amodiaquine in people with Malaria and Sickle Cell Crisis, run by London School of Hygiene and Tropical Medicine at 1 site 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 8 inclusion and 4 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 21 Mar 2014. 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 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Incidence of adverse events (time frame: 12 months). 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 NCT01319448, which also lists 1 linked publication.
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 21 Mar 2014.