MalariaPhase 4NCT00495508
Quinine vs. Artemether/Lumefantrine in Uncomplicated Malaria During Pregnancy
A Phase 4 study testing Quinine and artemether / lumefantrine in people with Malaria, run by Epicentre at 1 site in Uganda.
Trial summary
A) for the treatment of uncomplicated malaria during second and third trimester pregnancy to oral Quinine hydrochloride. The PCR-corrected adequate clinical and parasitological response (ACPR) on day 42 is considered as the primary efficacy criterion. Newborns will be followed for growth and development indicators. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Malaria
- What is being tested?
- Quinine and artemether / lumefantrine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteUganda
- Study dates
- Oct 2006to Jun 2009
- 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 Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Cohort Study:
- Weeks of pregnancy between 13 and 22 weeks
- Resident in Mbarara Municipality (radius of 15km from MNRH)
- Cohort study signed informed consent form
- Efficacy Study:
- Pregnant woman
Show all 9Show fewer
- Malaria infection, detected by microscopy, with P. falciparum (mixed or mono-infection)
- Age of gestation: 13 weeks and beyond
- Efficacy study signed informed consent form
Who cannot join
- Efficacy Study:
- P. falciparum parasitaemia above 250,000 parasites/μl
- Severe anaemia
- Signs or symptoms of severe/complicated malaria requiring parenteral treatment (WHO 2000)
- Known allergy to artemisinin derivatives, lumefantrine or quinine;
- Previous participation in the efficacy study
- Inability to attend the efficacy study follow-up schedule.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised, Open-label Non-inferiority Trial of Artemether-lumefantrine Versus Quinine for the Treatment of Uncomplicated Falciparum Malaria During Pregnancy, Mbarara, Uganda (2006-2007)
- for the treatment of uncomplicated malaria during second and third trimester pregnancy to oral Quinine hydrochloride. The PCR-corrected adequate clinical and parasitological response (ACPR) on day 42 is considered as the primary efficacy criterion. Newborns will be followed for growth and development indicators.
Read the detailed description
Study Title:
Efficacy and Safety of Quinine vs Artemether/Lumefantrine in uncomplicated malaria during pregnancy, Mbarara, Uganda (2006/2007).
Regulatory Status:
Investigational - Phase IV
Investigational Product and route:
- Quinine hydrochloride, oral route.
- Coartem® (Novartis Pharma AG, Basel, Switzerland), oral route.
Lead Investigator and Study Centre Primary objective - To establish that, in pregnant women with uncomplicated Plasmodium falciparum malaria, the PCR-adjusted efficacy of Artemether/Lumefantrine is not inferior to oral Quinine.
Secondary objectives
- To define the pharmacokinetics of the combination artemether-lumefantrine (AL) in the treatment of uncomplicated P. falciparum infections in the last two trimesters of pregnancy.
- To collect baseline data on maternal, obstetric and infant outcomes.
- To estimate the incidence of malaria infection, both microscopic and sub-microscopic (by PCR) during pregnancy.
- women attending Mbarara National Referral Hospital (MNRH) ante-natal clinic (ANC).
- Women with a positive blood smear during follow-up will be invited to participate in a non-inferiority, open, randomised, non- inferiority trial comparing the efficacy and tolerance of Coartem® (Artemether-Lumefantrine) for the treatment of uncomplicated malaria during second and third trimester pregnancy to oral Quinine hydrochloride. PCR-corrected adequate clinical and parasitological response (ACPR) on day 42 is considered as the primary efficacy criterion.
- Women with uncomplicated malaria from the efficacy study, will be followed to obtain an efficacy endpoint at 42 days OR at delivery, whichever timepoint is the last.
- Newborns will be followed monthly up to the age of 1 year.
Inclusion Criteria (Efficacy Study):
- Pregnant woman
- Malaria infection, detected by microscopy, with P. falciparum (mixed or mono-infection)
- Age of gestation: 13 weeks and beyond
- Efficacy study signed informed consent form
Exclusion Criteria (Efficacy Study):
- P. falciparum parasitaemia above 250,000 parasites/μl
- Severe anaemia
- Signs or symptoms of severe/complicated malaria requiring parenteral treatment (WHO 2000)
- Known allergy to artemisinin derivatives, lumefantrine or quinine;
- Previous participation in the efficacy study
- Inability to attend the efficacy study follow-up schedule.
Study drugs and Administration
- Group 1 (Active Control): Quinine hydrochloride (10 mg/Kg/8h for 7 days) administered orally.
- Group 2 (Test): Coartem®, fixed Artemether-Lumefantrine (20/120 mg) GMP manufactured by Novartis Pharma AG (Basel, Switzerland), 4 tablets twice a day for 3 days with 200 ml of milk tea at each dose .
Endpoints
- Primary efficacy endpoint: PCR-corrected adequate clinical and parasitological response (ACPR) on Day 42.
- Secondary efficacy endpoints:
- PCR-corrected(ACPR)at delivery
- Pharmacokinetic parameters
- Symptom clearance Time
- Proportion of patients who have fever cleared at Day 1, 2 and 3
- Safety endpoints:
- Incidence of any adverse events
- Pregnancy outcome
- Infant development during the first year of life
- Conditions
- Malaria
- Being tested
- Quinine, artemether / lumefantrine
- Keywords
- Quinine, Artemether, Lumefantrine, malaria, Uganda, Artemisinin- based combination therapy, pregnancy, Malaria In Pregnancy
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QuinineDrug
artemether / lumefantrineDrug
| Study group | Role | What they receive |
|---|---|---|
| Quinine | Active comparator | Not described Receives: Drug: Quinine |
| Arthemeter lumefantrine | Active comparator | Not described Receives: Drug: artemether / lumefantrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
PCR-corrected adequate clinical and parasitological response (ACPR) on Day 42 or at delivery.
Measured: 3 years
Secondary outcomes (5)
Pharmacokinetic parameters
Measured: 3.5 years
Incidence of adverse events
Measured: 3 years
Pregnancy outcome
Measured: 3.5 years
Infant development during the first year of life
Measured: 3 years
Histopathological findings in the placenta
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2007 (estimated)
- Study startOct 2006
- Primary completionJun 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Epicentre
- Sponsor type
- University, hospital or other
- Collaborators
- Medecins Sans Frontieres, Netherlands, University of Cape Town, Shoklo Malaria Research Unit
- Responsible party
- Sponsor
- Investigators
- Patrice Piola, MD, MPH, Principal investigator, EpicentrePhilippe J Guerin, MD, MPH, PhD, Study chair, EpicentreElizabeth Ashley, MB BS, Study chair, EpicentreRose McGready, MD, PhD, Study chair, Shoklo Malaria Research Unit (SMRU)François Nosten, MD, PhD, Study chair, SMRU
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00495508
- Sponsor's protocol ID
- Mba/06/MIP
- Status last verified
- Aug 2019
- First submitted
- 2 Jul 2007
- Last updated
- 3 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
De Beaudrap P, Turyakira E, Nabasumba C, Tumwebaze B, Piola P, Boum Ii Y, McGready R. Timing of malaria in pregnancy and impact on infant growth and morbidity: a cohort study in Uganda. Malar J. 2016 Feb 16;15:92. doi: 10.1186/s12936-016-1135-7.
PubMed 26879849De Beaudrap P, Turyakira E, White LJ, Nabasumba C, Tumwebaze B, Muehlenbachs A, Guerin PJ, Boum Y, McGready R, Piola P. Impact of malaria during pregnancy on pregnancy outcomes in a Ugandan prospective cohort with intensive malaria screening and prompt treatment. Malar J. 2013 Apr 24;12:139. doi: 10.1186/1475-2875-12-139.
PubMed 23617626Muehlenbachs A, Nabasumba C, McGready R, Turyakira E, Tumwebaze B, Dhorda M, Nyehangane D, Nalusaji A, Nosten F, Guerin PJ, Piola P. Artemether-lumefantrine to treat malaria in pregnancy is associated with reduced placental haemozoin deposition compared to quinine in a randomized controlled trial. Malar J. 2012 May 3;11:150. doi: 10.1186/1475-2875-11-150.
PubMed 22554092Piola P, Nabasumba C, Turyakira E, Dhorda M, Lindegardh N, Nyehangane D, Snounou G, Ashley EA, McGready R, Nosten F, Guerin PJ. Efficacy and safety of artemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial. Lancet Infect Dis. 2010 Nov;10(11):762-9. doi: 10.1016/S1473-3099(10)70202-4.
PubMed 20932805
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Open-label Non-inferiority Trial of Artemether-lumefantrine Versus Quinine for the Treatment of Uncomplicated Falciparum Malaria During Pregnancy, Mbarara, Uganda (2006-2007)
- ClinicalTrials.gov ID
- NCT00495508
- Acronym / sponsor ID
- Mba/06/MIP
- Conditions
- Malaria
- Keywords
- Quinine, Artemether, Lumefantrine, malaria, Uganda, Artemisinin- based combination therapy, pregnancy, Malaria In Pregnancy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- EpicentreUniversity, hospital or other
- Collaborators
- Medecins Sans Frontieres, Netherlands, University of Cape Town, Shoklo Malaria Research Unit
- Study start
- Oct 2006 (actual)
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 3 Jul 2007 (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.
- for the treatment of uncomplicated malaria during second and third trimester pregnancy to oral Quinine hydrochloride. The PCR-corrected adequate clinical and parasitological response (ACPR) on day 42 is considered as the primary efficacy criterion. Newborns will be followed for growth and development indicators.
Detailed description
Study Title:
Efficacy and Safety of Quinine vs Artemether/Lumefantrine in uncomplicated malaria during pregnancy, Mbarara, Uganda (2006/2007).
Regulatory Status:
Investigational - Phase IV
Investigational Product and route:
- Quinine hydrochloride, oral route.
- Coartem® (Novartis Pharma AG, Basel, Switzerland), oral route.
Lead Investigator and Study Centre Primary objective - To establish that, in pregnant women with uncomplicated Plasmodium falciparum malaria, the PCR-adjusted efficacy of Artemether/Lumefantrine is not inferior to oral Quinine.
Secondary objectives
- To define the pharmacokinetics of the combination artemether-lumefantrine (AL) in the treatment of uncomplicated P. falciparum infections in the last two trimesters of pregnancy.
- To collect baseline data on maternal, obstetric and infant outcomes.
- To estimate the incidence of malaria infection, both microscopic and sub-microscopic (by PCR) during pregnancy.
- women attending Mbarara National Referral Hospital (MNRH) ante-natal clinic (ANC).
- Women with a positive blood smear during follow-up will be invited to participate in a non-inferiority, open, randomised, non- inferiority trial comparing the efficacy and tolerance of Coartem® (Artemether-Lumefantrine) for the treatment of uncomplicated malaria during second and third trimester pregnancy to oral Quinine hydrochloride. PCR-corrected adequate clinical and parasitological response (ACPR) on day 42 is considered as the primary efficacy criterion.
- Women with uncomplicated malaria from the efficacy study, will be followed to obtain an efficacy endpoint at 42 days OR at delivery, whichever timepoint is the last.
- Newborns will be followed monthly up to the age of 1 year.
Inclusion Criteria (Efficacy Study):
- Pregnant woman
- Malaria infection, detected by microscopy, with P. falciparum (mixed or mono-infection)
- Age of gestation: 13 weeks and beyond
- Efficacy study signed informed consent form
Exclusion Criteria (Efficacy Study):
- P. falciparum parasitaemia above 250,000 parasites/μl
- Severe anaemia
- Signs or symptoms of severe/complicated malaria requiring parenteral treatment (WHO 2000)
- Known allergy to artemisinin derivatives, lumefantrine or quinine;
- Previous participation in the efficacy study
- Inability to attend the efficacy study follow-up schedule.
Study drugs and Administration
- Group 1 (Active Control): Quinine hydrochloride (10 mg/Kg/8h for 7 days) administered orally.
- Group 2 (Test): Coartem®, fixed Artemether-Lumefantrine (20/120 mg) GMP manufactured by Novartis Pharma AG (Basel, Switzerland), 4 tablets twice a day for 3 days with 200 ml of milk tea at each dose .
Endpoints
- Primary efficacy endpoint: PCR-corrected adequate clinical and parasitological response (ACPR) on Day 42.
- Secondary efficacy endpoints:
- PCR-corrected(ACPR)at delivery
- Pharmacokinetic parameters
- Symptom clearance Time
- Proportion of patients who have fever cleared at Day 1, 2 and 3
- Safety endpoints:
- Incidence of any adverse events
- Pregnancy outcome
- Infant development during the first year of life
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Quinine | Active comparator | Drug: Quinine |
| Arthemeter lumefantrine | Active comparator | Drug: artemether / lumefantrine |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Weeks of pregnancy between 13 and 22 weeks
- Resident in Mbarara Municipality (radius of 15km from MNRH)
- Cohort study signed informed consent form
- Pregnant woman
- Malaria infection, detected by microscopy, with P. falciparum (mixed or mono-infection)
Key exclusion criteria (7 listed)
- P. falciparum parasitaemia above 250,000 parasites/μl
- Severe anaemia
- Signs or symptoms of severe/complicated malaria requiring parenteral treatment (WHO 2000)
- Known allergy to artemisinin derivatives, lumefantrine or quinine;
- Previous participation in the efficacy study
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 |
|---|---|---|
| Quinine | Drug | Quinine |
| artemether / lumefantrine | Drug | Arthemeter lumefantrine |
Primary outcome
PCR-corrected adequate clinical and parasitological response (ACPR) on Day 42 or at delivery.
Time frame: 3 years
5 secondary outcomes
Pharmacokinetic parameters
Time frame: 3.5 years
Incidence of adverse events
Time frame: 3 years
Pregnancy outcome
Time frame: 3.5 years
Infant development during the first year of life
Time frame: 3 years
Histopathological findings in the placenta
Time frame: 4 years
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 3 Jun 2022.
- Derived from this study: PubMed 26879849De Beaudrap P, Turyakira E, Nabasumba C, Tumwebaze B, Piola P, Boum Ii Y, McGready R. Timing of malaria in pregnancy and impact on infant growth and morbidity: a cohort study in Uganda. Malar J. 2016 Feb 16;15:92. doi: 10.1186/s12936-016-1135-7.
- Derived from this study: PubMed 23617626De Beaudrap P, Turyakira E, White LJ, Nabasumba C, Tumwebaze B, Muehlenbachs A, Guerin PJ, Boum Y, McGready R, Piola P. Impact of malaria during pregnancy on pregnancy outcomes in a Ugandan prospective cohort with intensive malaria screening and prompt treatment. Malar J. 2013 Apr 24;12:139. doi: 10.1186/1475-2875-12-139.
- Derived from this study: PubMed 22554092Muehlenbachs A, Nabasumba C, McGready R, Turyakira E, Tumwebaze B, Dhorda M, Nyehangane D, Nalusaji A, Nosten F, Guerin PJ, Piola P. Artemether-lumefantrine to treat malaria in pregnancy is associated with reduced placental haemozoin deposition compared to quinine in a randomized controlled trial. Malar J. 2012 May 3;11:150. doi: 10.1186/1475-2875-11-150.
- Derived from this study: PubMed 20932805Piola P, Nabasumba C, Turyakira E, Dhorda M, Lindegardh N, Nyehangane D, Snounou G, Ashley EA, McGready R, Nosten F, Guerin PJ. Efficacy and safety of artemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial. Lancet Infect Dis. 2010 Nov;10(11):762-9. doi: 10.1016/S1473-3099(10)70202-4.
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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.
Patrice Piola, MD, MPH principal investigator
Epicentre
Philippe J Guerin, MD, MPH, PhD study chair
Epicentre
Elizabeth Ashley, MB BS study chair
Epicentre
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 Quinine and artemether / lumefantrine in people with Malaria, run by Epicentre 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 9 inclusion and 7 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 3 Jun 2022. 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 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?
PCR-corrected adequate clinical and parasitological response (ACPR) on Day 42 or at delivery. (time frame: 3 years). 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 NCT00495508, which also lists 4 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 3 Jun 2022.