Cerebral MalariaPhase 3NCT00124267
Efficacy of Intrarectal Versus Intravenous Quinine for the Treatment of Childhood Cerebral Malaria
A Phase 3 study testing Intrarectal quinine in people with Cerebral Malaria, run by Makerere University at 1 site in Uganda.
Trial summary
Cerebral malaria is the most lethal complication of P.falciparum infection with a mortality rate between 5 and 40%. Intravenous quinine remains the recommended treatment for cerebral malaria. However its administration is often not feasible due to lack of simple equipment or trained staff. Read more about this study
- Who is it for?
- Ages 6 months to 5 years
- Conditions the study is for
- Cerebral Malaria
- What is being tested?
- Intrarectal quinine
- How many people
- 108 participants
- Where
- 1 siteUganda
- Study dates
- Sep 2003to Jan 2004
- Phase
- Phase 3
- 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 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children aged 6 months to 5 years admitted to Mulago hospital during the study period who satisfy the World Health Organization (WHO) case definition of cerebral malaria (Unarousable coma lasting more than 30 minutes after a seizure, with peripheral asexual P.falciparum parasitaemia and absence of other causes of coma) and whose caretakers give informed consent.
Who cannot join
- Patients with diarrhea (more than 4 motions/24 hours)
- Any recent anal pathology (such as rectal bleeding, rectal prolapse)
- Documented quinine treatment in previous 48 hours.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy of Intrarectal Versus Intravenous Quinine for the Treatment of Childhood Cerebral Malaria: a Randomized Clinical Trial
Cerebral malaria is the most lethal complication of P.falciparum infection with a mortality rate between 5 and 40%. Intravenous quinine remains the recommended treatment for cerebral malaria. However its administration is often not feasible due to lack of simple equipment or trained staff. When referral is not possible, a viable alternative is needed. The intrarectal route is of interest in children since it is painless and simple. Studies of the efficacy of intrarectal quinine in the treatment of cerebral malaria are limited. The study aims to establish the efficacy of intrarectal quinine in the treatment of childhood cerebral malaria.
Read the detailed description
Cerebral malaria is the most lethal complication of P.falciparum infection with a mortality rate between 5 and 40%. Intravenous quinine remains the recommended treatment for cerebral malaria. However its administration is often not feasible due to lack of simple equipment or trained staff. When referral is not possible, a viable alternative is needed. The intrarectal route is of interest in children since it is painless and simple. A few studies in Francophone Africa have reported clinical efficacy and tolerance of intrarectal quinine. Although the studies were randomized trials, they were not blinded and did not use the WHO definition of cerebral malaria as selection criteria.
The current study aims to establish whether intrarectal quinine is as effective and as safe as intravenous quinine in the treatment of childhood cerebral malaria.
To address the shortcomings of the Francophone African studies, the investigators have designed a randomized, double blind placebo controlled clinical trial to include patients who meet the WHO definition of cerebral malaria.
Hypothesis:
Intrarectal quinine (15mg/kg every 8 hours) given to children with cerebral malaria, will lead to a shorter parasite clearance time (39.9 hours) than intravenous quinine (55.0 hours).
The investigators calculated a sample size of 54 patients in each group for 90% power and 95% confidence. In the calculation, the researchers assumed that the children receiving intrarectal quinine would have a mean parasite clearance time of 39.9 (SD 24.3) hours and those receiving intravenous quinine would have a mean parasite clearance time of 55.0(SD 24.3) hours (27.5% effect size), according to a study by Aceng, Byarugaba and Tumwine in the same hospital.
- Conditions
- Cerebral Malaria
- Being tested
- Intrarectal quinine
- Keywords
- Cerebral, malaria, intra-rectal, quinine, children, Uganda, efficacy, safety
- Medical subject headings
- Malaria, Cerebral, Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intrarectal quinineDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Parasite clearance time
Secondary outcomes (7)
Fever clearance time
Coma recovery time
Time to sit unsupported
Time to begin oral intake
Mortality
Neurological sequelae
Adverse drug events
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2005 (estimated)
- Study startSep 2003
- Study completionJan 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Cerebral 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 108 participants
Sponsor and investigators
- Lead sponsor
- Makerere University
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi-Synthelabo, Ministry of Health, Uganda
- Investigators
- Jane Achan, MBChB, Principal investigator, Department of Paediatrics and Child Health, Makerere University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00124267
- Sponsor's protocol ID
- 2001/HD11/524/RQ
- Status last verified
- Jul 2005
- First submitted
- 26 Jul 2005
- Last updated
- 4 Aug 2005
- Results posted
- No
Publications
Pussard E, Straczek C, Kabore I, Bicaba A, Balima-Koussoube T, Bouree P, Barennes H. Dose-dependent resorption of quinine after intrarectal administration to children with moderate Plasmodium falciparum malaria. Antimicrob Agents Chemother. 2004 Nov;48(11):4422-6. doi: 10.1128/AAC.48.11.4422-4426.2004.
PubMed 15504872Barennes H, Sterlingot H, Nagot N, Meda H, Kabore M, Sanou M, Nacro B, Bouree P, Pussard E. Intrarectal pharmacokinetics of two formulations of quinine in children with falciparum malaria. Eur J Clin Pharmacol. 2003 Feb;58(10):649-52. doi: 10.1007/s00228-002-0546-2. Epub 2003 Jan 29.
PubMed 12610739Barennes H, Munjakazi J, Verdier F, Clavier F, Pussard E. An open randomized clinical study of intrarectal versus infused Quinimax for the treatment of childhood cerebral malaria in Niger. Trans R Soc Trop Med Hyg. 1998 Jul-Aug;92(4):437-40. doi: 10.1016/s0035-9203(98)91083-5.
PubMed 9850403Aceng JR, Byarugaba JS, Tumwine JK. Rectal artemether versus intravenous quinine for the treatment of cerebral malaria in children in Uganda: randomised clinical trial. BMJ. 2005 Feb 12;330(7487):334. doi: 10.1136/bmj.330.7487.334.
PubMed 15705690Simoes EA, Peterson S, Gamatie Y, Kisanga FS, Mukasa G, Nsungwa-Sabiiti J, Were MW, Weber MW. Management of severely ill children at first-level health facilities in sub-Saharan Africa when referral is difficult. Bull World Health Organ. 2003;81(7):522-31. Epub 2003 Sep 3.
PubMed 12973645Nakibuuka V, Ndeezi G, Nakiboneka D, Ndugwa CM, Tumwine JK. Presumptive treatment with sulphadoxine-pyrimethamine versus weekly chloroquine for malaria prophylaxis in children with sickle cell anaemia in Uganda: a randomized controlled trial. Malar J. 2009 Oct 24;8:237. doi: 10.1186/1475-2875-8-237.
PubMed 19852829
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2005. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Intrarectal Versus Intravenous Quinine for the Treatment of Childhood Cerebral Malaria: a Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT00124267
- Acronym / sponsor ID
- 2001/HD11/524/RQ
- Conditions
- Cerebral Malaria
- Keywords
- Cerebral, malaria, intra-rectal, quinine, children, Uganda, efficacy, safety
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 108 participants
- Lead sponsor
- Makerere UniversityUniversity, hospital or other
- Collaborators
- Sanofi-Synthelabo, Ministry of Health, Uganda
- Study start
- Sep 2003
- Study completion
- Jan 2004
- First posted
- 27 Jul 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.
Cerebral malaria is the most lethal complication of P.falciparum infection with a mortality rate between 5 and 40%. Intravenous quinine remains the recommended treatment for cerebral malaria. However its administration is often not feasible due to lack of simple equipment or trained staff. When referral is not possible, a viable alternative is needed. The intrarectal route is of interest in children since it is painless and simple. Studies of the efficacy of intrarectal quinine in the treatment of cerebral malaria are limited. The study aims to establish the efficacy of intrarectal quinine in the treatment of childhood cerebral malaria.
Detailed description
Cerebral malaria is the most lethal complication of P.falciparum infection with a mortality rate between 5 and 40%. Intravenous quinine remains the recommended treatment for cerebral malaria. However its administration is often not feasible due to lack of simple equipment or trained staff. When referral is not possible, a viable alternative is needed. The intrarectal route is of interest in children since it is painless and simple. A few studies in Francophone Africa have reported clinical efficacy and tolerance of intrarectal quinine. Although the studies were randomized trials, they were not blinded and did not use the WHO definition of cerebral malaria as selection criteria.
The current study aims to establish whether intrarectal quinine is as effective and as safe as intravenous quinine in the treatment of childhood cerebral malaria.
To address the shortcomings of the Francophone African studies, the investigators have designed a randomized, double blind placebo controlled clinical trial to include patients who meet the WHO definition of cerebral malaria.
Hypothesis:
Intrarectal quinine (15mg/kg every 8 hours) given to children with cerebral malaria, will lead to a shorter parasite clearance time (39.9 hours) than intravenous quinine (55.0 hours).
The investigators calculated a sample size of 54 patients in each group for 90% power and 95% confidence. In the calculation, the researchers assumed that the children receiving intrarectal quinine would have a mean parasite clearance time of 39.9 (SD 24.3) hours and those receiving intravenous quinine would have a mean parasite clearance time of 55.0(SD 24.3) hours (27.5% effect size), according to a study by Aceng, Byarugaba and Tumwine in the same hospital.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 6 months to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Children aged 6 months to 5 years admitted to Mulago hospital during the study period who satisfy the World Health Organization (WHO) case definition of cerebral malaria (Unarousable coma lasting more than 30 minutes after a seizure, with peripheral asexual P.falciparum parasitaemia and absence of other causes of coma) and whose caretakers give informed consent.
Key exclusion criteria (3 listed)
- Patients with diarrhea (more than 4 motions/24 hours)
- Any recent anal pathology (such as rectal bleeding, rectal prolapse)
- Documented quinine treatment in previous 48 hours.
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 |
|---|---|---|
| Intrarectal quinine | Drug | – |
Primary outcome
Parasite clearance time
7 secondary outcomes
Fever clearance time
Coma recovery time
Time to sit unsupported
Time to begin oral intake
Mortality
Neurological sequelae
Adverse drug events
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2005.
- Background: PubMed 15504872Pussard E, Straczek C, Kabore I, Bicaba A, Balima-Koussoube T, Bouree P, Barennes H. Dose-dependent resorption of quinine after intrarectal administration to children with moderate Plasmodium falciparum malaria. Antimicrob Agents Chemother. 2004 Nov;48(11):4422-6. doi: 10.1128/AAC.48.11.4422-4426.2004.
- Background: PubMed 12610739Barennes H, Sterlingot H, Nagot N, Meda H, Kabore M, Sanou M, Nacro B, Bouree P, Pussard E. Intrarectal pharmacokinetics of two formulations of quinine in children with falciparum malaria. Eur J Clin Pharmacol. 2003 Feb;58(10):649-52. doi: 10.1007/s00228-002-0546-2. Epub 2003 Jan 29.
- Background: PubMed 9850403Barennes H, Munjakazi J, Verdier F, Clavier F, Pussard E. An open randomized clinical study of intrarectal versus infused Quinimax for the treatment of childhood cerebral malaria in Niger. Trans R Soc Trop Med Hyg. 1998 Jul-Aug;92(4):437-40. doi: 10.1016/s0035-9203(98)91083-5.
- Background: PubMed 15705690Aceng JR, Byarugaba JS, Tumwine JK. Rectal artemether versus intravenous quinine for the treatment of cerebral malaria in children in Uganda: randomised clinical trial. BMJ. 2005 Feb 12;330(7487):334. doi: 10.1136/bmj.330.7487.334.
- Background: PubMed 12973645Simoes EA, Peterson S, Gamatie Y, Kisanga FS, Mukasa G, Nsungwa-Sabiiti J, Were MW, Weber MW. Management of severely ill children at first-level health facilities in sub-Saharan Africa when referral is difficult. Bull World Health Organ. 2003;81(7):522-31. Epub 2003 Sep 3.
- Derived from this study: PubMed 19852829Nakibuuka V, Ndeezi G, Nakiboneka D, Ndugwa CM, Tumwine JK. Presumptive treatment with sulphadoxine-pyrimethamine versus weekly chloroquine for malaria prophylaxis in children with sickle cell anaemia in Uganda: a randomized controlled trial. Malar J. 2009 Oct 24;8:237. doi: 10.1186/1475-2875-8-237.
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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.
Jane Achan, MBChB principal investigator
Department of Paediatrics and Child Health, Makerere University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intrarectal quinine in people with Cerebral Malaria, run by Makerere University at 1 site in Uganda.
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 3 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 4 Aug 2005. 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 Uganda. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
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?
Parasite clearance time. 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 NCT00124267, which also lists 6 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 4 Aug 2005.