Efficacy of Fosmidomycin-Clindamycin for Treating Malaria in Gabonese Children

NCT ID: NCT00214643

Last Updated: 2009-02-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

160 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-06-30

Study Completion Date

2006-07-31

Brief Summary

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There is a necessity for the development of new malaria drugs. Some antibiotics are also effective against malaria parasites. Fosmidomycin is an antibiotic that has been shown to be effective against malaria, although it cannot achieve a total cure in all patients. Previous small studies have shown that in combination with clindamycin, an commonly used antibiotic, it is highly effective and safe when given for three days, leading to a total cure in most patients. The current study will evaluate its efficacy in a larger population in Gabon, and compare its effect with the generally used drug, sulfadoxine-pyrimethamine.

Detailed Description

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Fosmidomycin-clindamycin (30 mg/kg and 10 mg/kg) given twice daily for three days is an effective and safe combination of antibiotics which demonstrated good activity against malaria parasite in previous phase II studies in African children. In this phase III trial, the efficacy and safety of the combination will be evaluated in African children with uncomplicated P. falciparum malaria. A single dose of sulfadoxine-pyrimethamine, the standard antimalarial in Gabon, is used as comparator.

Conditions

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Malaria

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Fosmidomycin

30 mg/kg

Intervention Type DRUG

clindamycin

10 mg/kg

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Uncomplicated P. falciparum malaria
* P. falciparum asexual parasitaemia between 1,000/µL and 100,000/µL
* Body weight between 10 - 65 kg
* Ability to tolerate oral therapy
* Informed consent, oral assent of the child, if possible
* Residence in study area

Exclusion Criteria

* Adequate anti-malarial treatment within the previous 7 days
* Antibiotic treatment for the current infection
* Previous participation in this clinical trial
* Haemoglobin \< 7 g/dl
* Haematocrit \< 23 %
* Leucocyte count \> 15,000 /µL
* Mixed plasmodial infection
* Severe malaria (as defined by WHO)
* Any other severe underlying disease (cardiac, renal, hepatic diseases, malnutrition, known HIV infection)
* Concomitant disease masking assessment of response
* History of allergy or intolerance against trial medication
Minimum Eligible Age

3 Years

Maximum Eligible Age

14 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Albert Schweitzer Hospital

OTHER

Sponsor Role collaborator

Albert Schweitzer Hospital, Netherlands

UNKNOWN

Sponsor Role lead

Principal Investigators

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Saadou Issifou, MD

Role: PRINCIPAL_INVESTIGATOR

Albert Schweitzer Hospital

Locations

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Medical Research Unit, Lambaréné

Lambaréné, Moyen-Ogooué Province, Gabon

Site Status

Countries

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Gabon

References

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Kuemmerle HP, Murakawa T, Sakamoto H, Sato N, Konishi T, De Santis F. Fosmidomycin, a new phosphonic acid antibiotic. Part II: 1. Human pharmacokinetics. 2. Preliminary early phase IIa clinical studies. Int J Clin Pharmacol Ther Toxicol. 1985 Oct;23(10):521-8.

Reference Type BACKGROUND
PMID: 4066076 (View on PubMed)

Kuemmerle HP, Murakawa T, Soneoka K, Konishi T. Fosmidomycin: a new phosphonic acid antibiotic. Part I: Phase I tolerance studies. Int J Clin Pharmacol Ther Toxicol. 1985 Oct;23(10):515-20.

Reference Type BACKGROUND
PMID: 4066075 (View on PubMed)

Rohmer M, Knani M, Simonin P, Sutter B, Sahm H. Isoprenoid biosynthesis in bacteria: a novel pathway for the early steps leading to isopentenyl diphosphate. Biochem J. 1993 Oct 15;295 ( Pt 2)(Pt 2):517-24. doi: 10.1042/bj2950517.

Reference Type BACKGROUND
PMID: 8240251 (View on PubMed)

Kuzuyama T, Shizimu T, Takashi S and Seto H. Fosmidomycin, a specific inhibitor of 1-deoxy-D-xylulose 5-phosphate reductoisomerase in the nonmevalonate pathway of isoprenoid biosynthesis. Tetrahaedron Lett 1998;39:7913-6

Reference Type BACKGROUND

Zeidler J, Schwender J, Müller C, et al. Inhibition of the non-mevalonate 1-deoxy-D-xylulose-5-phosphate pathway of plant isoprenoid biosynthesis by fosmidomycin. Z Naturforsch 1998;53:980-6

Reference Type BACKGROUND

Lois LM, Campos N, Putra SR, Danielsen K, Rohmer M, Boronat A. Cloning and characterization of a gene from Escherichia coli encoding a transketolase-like enzyme that catalyzes the synthesis of D-1-deoxyxylulose 5-phosphate, a common precursor for isoprenoid, thiamin, and pyridoxol biosynthesis. Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2105-10. doi: 10.1073/pnas.95.5.2105.

Reference Type BACKGROUND
PMID: 9482846 (View on PubMed)

Takahashi S, Kuzuyama T, Watanabe H, Seto H. A 1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzing the formation of 2-C-methyl-D-erythritol 4-phosphate in an alternative nonmevalonate pathway for terpenoid biosynthesis. Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9879-84. doi: 10.1073/pnas.95.17.9879.

Reference Type BACKGROUND
PMID: 9707569 (View on PubMed)

Jomaa H, Wiesner J, Sanderbrand S, Altincicek B, Weidemeyer C, Hintz M, Turbachova I, Eberl M, Zeidler J, Lichtenthaler HK, Soldati D, Beck E. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science. 1999 Sep 3;285(5433):1573-6. doi: 10.1126/science.285.5433.1573.

Reference Type BACKGROUND
PMID: 10477522 (View on PubMed)

Kohler S, Delwiche CF, Denny PW, Tilney LG, Webster P, Wilson RJ, Palmer JD, Roos DS. A plastid of probable green algal origin in Apicomplexan parasites. Science. 1997 Mar 7;275(5305):1485-9. doi: 10.1126/science.275.5305.1485.

Reference Type BACKGROUND
PMID: 9045615 (View on PubMed)

Fichera ME, Roos DS. A plastid organelle as a drug target in apicomplexan parasites. Nature. 1997 Nov 27;390(6658):407-9. doi: 10.1038/37132.

Reference Type BACKGROUND
PMID: 9389481 (View on PubMed)

Borrmann S, Adegnika AA, Matsiegui PB, Issifou S, Schindler A, Mawili-Mboumba DP, Baranek T, Wiesner J, Jomaa H, Kremsner PG. Fosmidomycin-clindamycin for Plasmodium falciparum Infections in African children. J Infect Dis. 2004 Mar 1;189(5):901-8. doi: 10.1086/381785. Epub 2004 Feb 16.

Reference Type BACKGROUND
PMID: 14976608 (View on PubMed)

Borrmann S, Issifou S, Esser G, Adegnika AA, Ramharter M, Matsiegui PB, Oyakhirome S, Mawili-Mboumba DP, Missinou MA, Kun JF, Jomaa H, Kremsner PG. Fosmidomycin-clindamycin for the treatment of Plasmodium falciparum malaria. J Infect Dis. 2004 Nov 1;190(9):1534-40. doi: 10.1086/424603. Epub 2004 Sep 21.

Reference Type BACKGROUND
PMID: 15478056 (View on PubMed)

Shulman CE, Dorman EK, Cutts F, Kawuondo K, Bulmer JN, Peshu N, Marsh K. Intermittent sulphadoxine-pyrimethamine to prevent severe anaemia secondary to malaria in pregnancy: a randomised placebo-controlled trial. Lancet. 1999 Feb 20;353(9153):632-6. doi: 10.1016/s0140-6736(98)07318-8.

Reference Type BACKGROUND
PMID: 10030329 (View on PubMed)

Schellenberg 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.

Reference Type BACKGROUND
PMID: 11377597 (View on PubMed)

Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg. 2000 Apr;94 Suppl 1:S1-90. No abstract available.

Reference Type BACKGROUND
PMID: 11103309 (View on PubMed)

Related Links

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http://www.malaria.org

General information on malaria at the website of the Malaria International Foundation

http://www.lambarene.org

Homepage of the Medical Research Unit, Lambaréné

Other Identifiers

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06/2005/FOS-CLIN/SP

Identifier Type: -

Identifier Source: org_study_id

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