Malaria,FalciparumPhase 4ALU-PQNCT03241901
"Prolonging the Therapeutic Life Span of Artemisinin-based Combination Therapies (ACT) in Bagamoyo District, Tanzania"
A Phase 4 study testing Artemether-Lumefantrine Tab 20-120mg and Primaquine Phosphate 0.25 mg/kg in people with Malaria,Falciparum, run by Muhimbili University of Health and Allied Sciences at 2 sites in Tanzania.
Trial summary
This clinical trial evaluates the advantage of prolonging the therapeutic life span of Artemether-lumefantrine from 3 days to 6 days, and addition of single low dose of Primaquine 0.25mg/kg. Read more about this study
- Who is it for?
- Ages 1 year to 65 years
- Conditions the study is for
- Malaria,Falciparum
- What is being tested?
- Artemether-Lumefantrine Tab 20-120mg and Primaquine Phosphate 0.25 mg/kg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 280 participants
- Where
- 2 sitesTanzania
- Study dates
- 27 Jul 2017to 17 Feb 2018
- 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 1 year to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age more than 1 year and less than 65 years.
- Weight 10 kg and above;
- Body temperature ≥37.5°C or history of fever in the last 24 hours;
- Microscopy determined asexual P. falciparum mono-infection regardless of parasitemia
- Normal - corrected QT Interval in Baseline ECG of less than 440ms in male and 460ms in females
Who cannot join
- Symptoms/signs of severe malaria or danger signs;
- Pregnancy, Breastfeeding or unwilling to practice birth control during participation in the study.
- Known allergy to study medications;
- Hb <8 g/dl;
- Reported antimalarial intake within last 2 weeks;
- On regular medication, which may interfere with antimalarial pharmacokinetics and
- Blood transfusion within last 90 days.
Trial locations and contacts
2 sites in 1 country.
Tanzania2 sites
Fukayosi Dispensary
Bagamoyo, Pwani Region, +255
Yombo Dispensary
Bagamoyo, Yombo, +255
About this study
Official title: "Aiming at Prolonging the Therapeutic Life Span of Artemisinin-based Combination Therapies (ACT) in an Era of Imminent Plasmodium Falciparum Resistance in Bagamoyo District, Tanzania - New Strategies With Old Tools"
This clinical trial evaluates the advantage of prolonging the therapeutic life span of Artemether-lumefantrine from 3 days to 6 days, and addition of single low dose of Primaquine 0.25mg/kg. The study will have two arms, one that will receive standard treatment of uncomplicated malaria with Artemether-lumefantrine, and the other arm will receive the prolonged dose of 6 days together with single low dose primaquine. This approach is expected to provide strategies for malaria control in an era of imminent Plasmodium falciparum resistance.
Read the detailed description
Despite documented high cure rates of ACT in Tanzania, and Africa elsewhere, clinical trials conducted in Tanzania with Swedish International Development cooperation Agency (SIDA) and Swedish Research Council support, provide evidence for in vivo selection of lumefantrine tolerant/resistant parasites among recurrent infections. Similarly, molecular epidemiology studies from Bagamoyo District, Tanzania, have shown temporal selection of lumefantrine associated genetic tolerance/resistance markers in the parasite population following wide scale use of Artemether-lumefantrine, but without signs of compromised treatment efficacy.
During the last decade, and despite the documented rapid microscopy determined parasite clearance of artemether-lumefantrine in Bagamoyo District, interest has developed in understanding the observation of high residual polymerase chain reaction (PCR) determined positivity rate on day 3 after supervised artemether-lumefantrine treatment in the magnitude of almost 30% in previous assessments from 2015. Using deep sequencing approaches studies have recently detected PCR determined delayed parasite clearance curves in P. falciparum sub-populations in Bagamoyo District. The clearance times by PCR of these sub-populations were similar to artemisinin resistant parasites in Myanmar as assessed by microscopy, but the former did, importantly, not harbor any of the described mutations in Kelch13 propeller associated with artemisinin resistance. However, these Tanzanian parasite sub-populations need to be further studied and characterized since they may provide important clues to the understanding of artemisinin survival strategies among the East African P. falciparum parasite population.
Taken together, longitudinal clinical and molecular data described above from Tanzania, East Africa, extending from pre-ACT implementation, (before 2006), to a decade of wide scale artemether-lumefantrine use in Bagamoyo district, provide evidence for declining susceptibility to ACT, both to artemether and lumefantrine, among the P. falciparum population. These parasites ("last man standing") that survived 10 years of ACT exposure have indeed shown excellent survival instincts and may thus be particularly resistant prone. However, if P. falciparum resistance to ACT develops in Africa, this will have devastating effects on malaria morbidity and mortality and may swiftly ruin the improvements the global malaria community achieved during the past decade with ACT as a key component for success.
Based on the above the investigators suggest prolonged treatment with ACT and addition of transmission blocking treatment using a single low dose of primaquine administered on the last day of ACT treatment.
- Conditions
- Malaria,Falciparum
- Being tested
- Artemether-Lumefantrine Tab 20-120mg, Primaquine Phosphate 0.25 mg/kg, Placebo
- Keywords
- Artemether-Lumefantrine, Primaquine
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artemether-Lumefantrine Tab 20-120mgDrug
Also called ALU
Artemether-Lumefantrine Tablet 20-120mg
Primaquine Phosphate 0.25 mg/kgDrug
Also called PQ
Primaquine Phosphate 0.25 mg/kg
PlaceboOther
Also called Placebo for Artemether Lumefantrine + Primaquine Phosphate
Aqueous solution prepared to mimic the taste of the intervention drug.
| Study group | Role | What they receive |
|---|---|---|
| 3 Days Artemether-Lumefantrine + Placebo | Active comparator | Oral tablets of artemether-lumefantrine (20-120mg):
1. tablet for 5-14kg;
2. tablets for 15-24 kg;
3. tables for 25 - 34kg and
4. tablets for above 35 Kg. The full course of treatment is 6-doses for 3 days given twice daily, at 0, 8, 24, 36, 48, 60 with the dose being given as directly observed therapy.
Oral placebo after completion of the standard 3 days-six dose regimen. A fatty snack (biscuits) will be administered together with all artemether-lumefantrine doses to optimize absorption. Receives: Drug: Artemether-Lumefantrine Tab 20-120mg; Other: Placebo |
| 6Days Artemether/Lumefantrine+Primaquine | Experimental | Artemether-lumefantrine (20-120mg) twice daily for 6 days according to body weight as in the active comparator arm.
And in addition to that, , a single 0.25 mg/kg primaquine dose (Primaquine phosphate) will be administered concomitantly with the last (i.e. twelfth) artemether-lumefantrine dose. Primaquine will be prepared and administered in an aqueous solution. Receives: Drug: Artemether-Lumefantrine Tab 20-120mg; Drug: Primaquine Phosphate 0.25 mg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parasite Clearance Times
Proportion of PCR detectable parasitemia on Day 5
Measured: 5 Days
Parasite Clearance Times
Proportion of PCR detectable parasitemia on Day 7
Measured: 7 Days
Secondary outcomes (6)
Gametocyte Clearance
PCR determined gametocyte carriage/clearance times
Measured: 42 Days
Cure Rate
Crude and PCR corrected cure rates by day 28
Measured: 28 Days
Genetic Markers of Drug Resistance
Selection of genetic drug resistance markers during the early treatment phase
Measured: 6 Days
Pharmacokinetics
Area under the plasma concentration versus time curve (AUC) of Artemether-lumefantrine
Measured: 7 Days
Peak Plasma Concentration (Cmax)
Peak Plasma Concentration (Cmax) of Lumefantrine measured for 28 days
Measured: At hours, -1, 0 ,2 ,4 ,12, 24, 36, 40, 48, 52, 60, 72, 84, 88, 96, 100, 108,120, 132, 134, 136 ,144, 168, 192, 240, 336, 504 and 672
Day 7 plasma lumefantrine
Day 7 plasma lumefantrine concentrations in the respective arms
Measured: 7 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2017
- Study start27 Jul 2017
- Primary completion28 Dec 2017
- Study completion17 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for Malaria,FalciparumStudies 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 280 participants (actual)
Sponsor and investigators
- Lead sponsor
- Muhimbili University of Health and Allied Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Uppsala University, Karolinska Institutet, The University of Western Australia
- Responsible party
- Principal investigator, Dr. Lwidiko Edward, Muhimbili University of Health and Allied Sciences
- Investigators
- Lwidiko E Mhamilawa, MD, Principal investigator, Muhimbili University of Health and Allied SciencesAndreas Martensson, PhD, Study chair, Uppsala University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03241901
- Sponsor's protocol ID
- No. 01.05.2017
- Acronym
- ALU-PQ
- Status last verified
- Mar 2018
- First submitted
- 5 Jul 2017
- Last updated
- 27 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sisowath C, Stromberg J, Martensson A, Msellem M, Obondo C, Bjorkman A, Gil JP. In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem). J Infect Dis. 2005 Mar 15;191(6):1014-7. doi: 10.1086/427997. Epub 2005 Feb 8.
PubMed 15717281Martensson A, Stromberg J, Sisowath C, Msellem MI, Gil JP, Montgomery SM, Olliaro P, Ali AS, Bjorkman A. Efficacy of artesunate plus amodiaquine versus that of artemether-lumefantrine for the treatment of uncomplicated childhood Plasmodium falciparum malaria in Zanzibar, Tanzania. Clin Infect Dis. 2005 Oct 15;41(8):1079-86. doi: 10.1086/444460. Epub 2005 Sep 13.
PubMed 16163624Malmberg M, Ngasala B, Ferreira PE, Larsson E, Jovel I, Hjalmarsson A, Petzold M, Premji Z, Gil JP, Bjorkman A, Martensson A. Temporal trends of molecular markers associated with artemether-lumefantrine tolerance/resistance in Bagamoyo district, Tanzania. Malar J. 2013 Mar 18;12:103. doi: 10.1186/1475-2875-12-103.
PubMed 23506218Mideo N, Bailey JA, Hathaway NJ, Ngasala B, Saunders DL, Lon C, Kharabora O, Jamnik A, Balasubramanian S, Bjorkman A, Martensson A, Meshnick SR, Read AF, Juliano JJ. A deep sequencing tool for partitioning clearance rates following antimalarial treatment in polyclonal infections. Evol Med Public Health. 2016 Jan 27;2016(1):21-36. doi: 10.1093/emph/eov036.
PubMed 26817485Mwaiswelo R, Ngasala BE, Jovel I, Gosling R, Premji Z, Poirot E, Mmbando BP, Bjorkman A, Martensson A. Safety of a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. Malar J. 2016 Jun 10;15:316. doi: 10.1186/s12936-016-1341-3.
PubMed 27287612R. Mwaiswelo, B. Ngasala, I. Jovel, W. Xu, and M. Malmberg, "Occurrence of day 3 submicroscopic Plasmodium falciparum parasitemia before and after implementation of artemether-lumefantrine treatment policy in Tanzania .," Dar Es Salaam, 2016
Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NP, Lindegardh N, Socheat D, White NJ. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009 Jul 30;361(5):455-67. doi: 10.1056/NEJMoa0808859.
PubMed 19641202Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois AC, Khim N, Kim S, Duru V, Bouchier C, Ma L, Lim P, Leang R, Duong S, Sreng S, Suon S, Chuor CM, Bout DM, Menard S, Rogers WO, Genton B, Fandeur T, Miotto O, Ringwald P, Le Bras J, Berry A, Barale JC, Fairhurst RM, Benoit-Vical F, Mercereau-Puijalon O, Menard D. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature. 2014 Jan 2;505(7481):50-5. doi: 10.1038/nature12876. Epub 2013 Dec 18.
PubMed 24352242Witkowski B, Amaratunga C, Khim N, Sreng S, Chim P, Kim S, Lim P, Mao S, Sopha C, Sam B, Anderson JM, Duong S, Chuor CM, Taylor WR, Suon S, Mercereau-Puijalon O, Fairhurst RM, Menard D. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies. Lancet Infect Dis. 2013 Dec;13(12):1043-9. doi: 10.1016/S1473-3099(13)70252-4. Epub 2013 Sep 11.
PubMed 24035558Straimer J, Gnadig NF, Witkowski B, Amaratunga C, Duru V, Ramadani AP, Dacheux M, Khim N, Zhang L, Lam S, Gregory PD, Urnov FD, Mercereau-Puijalon O, Benoit-Vical F, Fairhurst RM, Menard D, Fidock DA. Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science. 2015 Jan 23;347(6220):428-31. doi: 10.1126/science.1260867. Epub 2014 Dec 11.
PubMed 25502314Malmberg M, Ferreira PE, Tarning J, Ursing J, Ngasala B, Bjorkman A, Martensson A, Gil JP. Plasmodium falciparum drug resistance phenotype as assessed by patient antimalarial drug levels and its association with pfmdr1 polymorphisms. J Infect Dis. 2013 Mar 1;207(5):842-7. doi: 10.1093/infdis/jis747. Epub 2012 Dec 5.
PubMed 23225895Linder E, Lundin M, Thors C, Lebbad M, Winiecka-Krusnell J, Helin H, Leiva B, Isola J, Lundin J. Web-based virtual microscopy for parasitology: a novel tool for education and quality assurance. PLoS Negl Trop Dis. 2008;2(10):e315. doi: 10.1371/journal.pntd.0000315. Epub 2008 Oct 22.
PubMed 18941514Lundin M, Szymas J, Linder E, Beck H, de Wilde P, van Krieken H, Garcia Rojo M, Moreno I, Ariza A, Tuzlali S, Dervisoglu S, Helin H, Lehto VP, Lundin J. A European network for virtual microscopy--design, implementation and evaluation of performance. Virchows Arch. 2009 Apr;454(4):421-9. doi: 10.1007/s00428-009-0749-3. Epub 2009 Mar 12.
PubMed 19280223Aydin-Schmidt B, Xu W, Gonzalez IJ, Polley SD, Bell D, Shakely D, Msellem MI, Bjorkman A, Martensson A. Loop mediated isothermal amplification (LAMP) accurately detects malaria DNA from filter paper blood samples of low density parasitaemias. PLoS One. 2014 Aug 8;9(8):e103905. doi: 10.1371/journal.pone.0103905. eCollection 2014.
PubMed 25105591Cook J, Aydin-Schmidt B, Gonzalez IJ, Bell D, Edlund E, Nassor MH, Msellem M, Ali A, Abass AK, Martensson A, Bjorkman A. Loop-mediated isothermal amplification (LAMP) for point-of-care detection of asymptomatic low-density malaria parasite carriers in Zanzibar. Malar J. 2015 Jan 28;14:43. doi: 10.1186/s12936-015-0573-y.
PubMed 25627037
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "Aiming at Prolonging the Therapeutic Life Span of Artemisinin-based Combination Therapies (ACT) in an Era of Imminent Plasmodium Falciparum Resistance in Bagamoyo District, Tanzania - New Strategies With Old Tools"
- ClinicalTrials.gov ID
- NCT03241901
- Acronym / sponsor ID
- ALU-PQ / No. 01.05.2017
- Conditions
- Malaria,Falciparum
- Keywords
- Artemether-Lumefantrine, Primaquine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 280 participants (actual)
- Lead sponsor
- Muhimbili University of Health and Allied SciencesUniversity, hospital or other
- Collaborators
- Uppsala University, Karolinska Institutet, The University of Western Australia
- Study start
- 27 Jul 2017 (actual)
- Primary completion
- 28 Dec 2017 (actual)
- Study completion
- 17 Feb 2018 (actual)
- First posted
- 8 Aug 2017 (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.
This clinical trial evaluates the advantage of prolonging the therapeutic life span of Artemether-lumefantrine from 3 days to 6 days, and addition of single low dose of Primaquine 0.25mg/kg. The study will have two arms, one that will receive standard treatment of uncomplicated malaria with Artemether-lumefantrine, and the other arm will receive the prolonged dose of 6 days together with single low dose primaquine. This approach is expected to provide strategies for malaria control in an era of imminent Plasmodium falciparum resistance.
Detailed description
Despite documented high cure rates of ACT in Tanzania, and Africa elsewhere, clinical trials conducted in Tanzania with Swedish International Development cooperation Agency (SIDA) and Swedish Research Council support, provide evidence for in vivo selection of lumefantrine tolerant/resistant parasites among recurrent infections. Similarly, molecular epidemiology studies from Bagamoyo District, Tanzania, have shown temporal selection of lumefantrine associated genetic tolerance/resistance markers in the parasite population following wide scale use of Artemether-lumefantrine, but without signs of compromised treatment efficacy.
During the last decade, and despite the documented rapid microscopy determined parasite clearance of artemether-lumefantrine in Bagamoyo District, interest has developed in understanding the observation of high residual polymerase chain reaction (PCR) determined positivity rate on day 3 after supervised artemether-lumefantrine treatment in the magnitude of almost 30% in previous assessments from 2015. Using deep sequencing approaches studies have recently detected PCR determined delayed parasite clearance curves in P. falciparum sub-populations in Bagamoyo District. The clearance times by PCR of these sub-populations were similar to artemisinin resistant parasites in Myanmar as assessed by microscopy, but the former did, importantly, not harbor any of the described mutations in Kelch13 propeller associated with artemisinin resistance. However, these Tanzanian parasite sub-populations need to be further studied and characterized since they may provide important clues to the understanding of artemisinin survival strategies among the East African P. falciparum parasite population.
Taken together, longitudinal clinical and molecular data described above from Tanzania, East Africa, extending from pre-ACT implementation, (before 2006), to a decade of wide scale artemether-lumefantrine use in Bagamoyo district, provide evidence for declining susceptibility to ACT, both to artemether and lumefantrine, among the P. falciparum population. These parasites ("last man standing") that survived 10 years of ACT exposure have indeed shown excellent survival instincts and may thus be particularly resistant prone. However, if P. falciparum resistance to ACT develops in Africa, this will have devastating effects on malaria morbidity and mortality and may swiftly ruin the improvements the global malaria community achieved during the past decade with ACT as a key component for success.
Based on the above the investigators suggest prolonged treatment with ACT and addition of transmission blocking treatment using a single low dose of primaquine administered on the last day of ACT treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 3 Days Artemether-Lumefantrine + Placebo | Active comparator | Drug: Artemether-Lumefantrine Tab 20-120mg, Other: PlaceboOral tablets of artemether-lumefantrine (20-120mg): 1. tablet for 5-14kg; 2. tablets for 15-24 kg; 3. tables for 25 - 34kg and 4. tablets for above 35 Kg. The full course of treatment is 6-doses for 3 days given twice daily, at 0, 8, 24, 36, 48, 60 with the dose being given as directly observed therapy. Oral placebo after completion of the standard 3 days-six dose regimen. A fatty snack (biscuits) will be administered together with all artemether-lumefantrine doses to optimize absorption. |
| 6Days Artemether/Lumefantrine+Primaquine | Experimental | Drug: Artemether-Lumefantrine Tab 20-120mg, Drug: Primaquine Phosphate 0.25 mg/kgArtemether-lumefantrine (20-120mg) twice daily for 6 days according to body weight as in the active comparator arm. And in addition to that, , a single 0.25 mg/kg primaquine dose (Primaquine phosphate) will be administered concomitantly with the last (i.e. twelfth) artemether-lumefantrine dose. Primaquine will be prepared and administered in an aqueous solution. |
Who may qualify
- Ages
- 1 year to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Age more than 1 year and less than 65 years.
- Weight 10 kg and above;
- Body temperature ≥37.5°C or history of fever in the last 24 hours;
- Microscopy determined asexual P. falciparum mono-infection regardless of parasitemia
- Normal - corrected QT Interval in Baseline ECG of less than 440ms in male and 460ms in females
Key exclusion criteria (7 listed)
- Symptoms/signs of severe malaria or danger signs;
- Pregnancy, Breastfeeding or unwilling to practice birth control during participation in the study.
- Known allergy to study medications;
- Hb <8 g/dl;
- Reported antimalarial intake within last 2 weeks;
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 |
|---|---|---|
| Artemether-Lumefantrine Tab 20-120mgAlso: ALUArtemether-Lumefantrine Tablet 20-120mg | Drug | 3 Days Artemether-Lumefantrine + Placebo, 6Days Artemether/Lumefantrine+Primaquine |
| Primaquine Phosphate 0.25 mg/kgAlso: PQPrimaquine Phosphate 0.25 mg/kg | Drug | 6Days Artemether/Lumefantrine+Primaquine |
| PlaceboAlso: Placebo for Artemether Lumefantrine + Primaquine PhosphateAqueous solution prepared to mimic the taste of the intervention drug. | Other | 3 Days Artemether-Lumefantrine + Placebo |
Primary outcome
Parasite Clearance Times
Time frame: 5 Days
Proportion of PCR detectable parasitemia on Day 5
Parasite Clearance Times
Time frame: 7 Days
Proportion of PCR detectable parasitemia on Day 7
6 secondary outcomes
Gametocyte Clearance
Time frame: 42 Days
Cure Rate
Time frame: 28 Days
Genetic Markers of Drug Resistance
Time frame: 6 Days
Pharmacokinetics
Time frame: 7 Days
Peak Plasma Concentration (Cmax)
Time frame: At hours, -1, 0 ,2 ,4 ,12, 24, 36, 40, 48, 52, 60, 72, 84, 88, 96, 100, 108,120, 132, 134, 136 ,144, 168, 192, 240, 336, 504 and 672
Day 7 plasma lumefantrine
Time frame: 7 Days
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 27 Mar 2018.
- Background: PubMed 15717281Sisowath C, Stromberg J, Martensson A, Msellem M, Obondo C, Bjorkman A, Gil JP. In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem). J Infect Dis. 2005 Mar 15;191(6):1014-7. doi: 10.1086/427997. Epub 2005 Feb 8.
- Background: PubMed 16163624Martensson A, Stromberg J, Sisowath C, Msellem MI, Gil JP, Montgomery SM, Olliaro P, Ali AS, Bjorkman A. Efficacy of artesunate plus amodiaquine versus that of artemether-lumefantrine for the treatment of uncomplicated childhood Plasmodium falciparum malaria in Zanzibar, Tanzania. Clin Infect Dis. 2005 Oct 15;41(8):1079-86. doi: 10.1086/444460. Epub 2005 Sep 13.
- Background: PubMed 23506218Malmberg M, Ngasala B, Ferreira PE, Larsson E, Jovel I, Hjalmarsson A, Petzold M, Premji Z, Gil JP, Bjorkman A, Martensson A. Temporal trends of molecular markers associated with artemether-lumefantrine tolerance/resistance in Bagamoyo district, Tanzania. Malar J. 2013 Mar 18;12:103. doi: 10.1186/1475-2875-12-103.
- Background: PubMed 26817485Mideo N, Bailey JA, Hathaway NJ, Ngasala B, Saunders DL, Lon C, Kharabora O, Jamnik A, Balasubramanian S, Bjorkman A, Martensson A, Meshnick SR, Read AF, Juliano JJ. A deep sequencing tool for partitioning clearance rates following antimalarial treatment in polyclonal infections. Evol Med Public Health. 2016 Jan 27;2016(1):21-36. doi: 10.1093/emph/eov036.
- Background: PubMed 27287612Mwaiswelo R, Ngasala BE, Jovel I, Gosling R, Premji Z, Poirot E, Mmbando BP, Bjorkman A, Martensson A. Safety of a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. Malar J. 2016 Jun 10;15:316. doi: 10.1186/s12936-016-1341-3.
- BackgroundR. Mwaiswelo, B. Ngasala, I. Jovel, W. Xu, and M. Malmberg, "Occurrence of day 3 submicroscopic Plasmodium falciparum parasitemia before and after implementation of artemether-lumefantrine treatment policy in Tanzania .," Dar Es Salaam, 2016
- Background: PubMed 19641202Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NP, Lindegardh N, Socheat D, White NJ. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009 Jul 30;361(5):455-67. doi: 10.1056/NEJMoa0808859.
- Background: PubMed 24352242Ariey F, Witkowski B, Amaratunga C, Beghain J, Langlois AC, Khim N, Kim S, Duru V, Bouchier C, Ma L, Lim P, Leang R, Duong S, Sreng S, Suon S, Chuor CM, Bout DM, Menard S, Rogers WO, Genton B, Fandeur T, Miotto O, Ringwald P, Le Bras J, Berry A, Barale JC, Fairhurst RM, Benoit-Vical F, Mercereau-Puijalon O, Menard D. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature. 2014 Jan 2;505(7481):50-5. doi: 10.1038/nature12876. Epub 2013 Dec 18.
- Background: PubMed 24035558Witkowski B, Amaratunga C, Khim N, Sreng S, Chim P, Kim S, Lim P, Mao S, Sopha C, Sam B, Anderson JM, Duong S, Chuor CM, Taylor WR, Suon S, Mercereau-Puijalon O, Fairhurst RM, Menard D. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies. Lancet Infect Dis. 2013 Dec;13(12):1043-9. doi: 10.1016/S1473-3099(13)70252-4. Epub 2013 Sep 11.
- Background: PubMed 25502314Straimer J, Gnadig NF, Witkowski B, Amaratunga C, Duru V, Ramadani AP, Dacheux M, Khim N, Zhang L, Lam S, Gregory PD, Urnov FD, Mercereau-Puijalon O, Benoit-Vical F, Fairhurst RM, Menard D, Fidock DA. Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science. 2015 Jan 23;347(6220):428-31. doi: 10.1126/science.1260867. Epub 2014 Dec 11.
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- "WHO World Malaria Report 2015," Geneva, Switzerland, 2015Link provided by the sponsor.
- WHO guidelines for the treatment of malaria 2015, 3rd Edition. Geneva, Switzerland, 2015Link provided by the sponsor.
- PRESIDENT'S MALARIA INITIATIVE Tanzania Malaria Operational Plan FY 2015Link provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Lwidiko E Mhamilawa, MD principal investigator
Muhimbili University of Health and Allied Sciences
Andreas Martensson, PhD study chair
Uppsala University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Artemether-Lumefantrine Tab 20-120mg and Primaquine Phosphate 0.25 mg/kg in people with Malaria,Falciparum, run by Muhimbili University of Health and Allied Sciences at 2 sites in Tanzania.
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 5 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 27 Mar 2018. 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 Tanzania. 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?
Parasite Clearance Times (time frame: 5 Days). 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 NCT03241901, which also lists 24 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 27 Mar 2018.