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Treatment of Malaria With Quinine Plus Sulfadoxine-Pyrimethamine
This study has been completed.
Sponsors and Collaborators: Albert Schweitzer Hospital, Netherlands
Medical Research Unit, Lambaréné
Information provided by: Albert Schweitzer Hospital, Netherlands
ClinicalTrials.gov Identifier: NCT00167739
  Purpose

Quinine remains the treatment of choice of hospitalised malaria cases. The long treatment duration of 7 days, and adverse reactions often hamper its adequate use. Reducing the treatment duration by adding sulfadoxine-pyrimethamine may enhance compliance and reduce side effects.

The efficacy of a 3-day treatment of quinine plus sulfadoxine-pyrimethamine for the treatment of hospitalised, uncomplicated malaria cases was assessed.


Condition Intervention Phase
Malaria
Drug: Quinine plus sulfadoxine-pyrimethamine
Phase IV

MedlinePlus related topics: Malaria
Drug Information available for: Pyrimethamine Sulfadoxine Fansidar Quinine Quinine bisulfate Quinine hydrochloride Quinine sulfate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: Short Course of Quinine Plus a Single Dose of Sulphadoxine-Pyrimethamine for Plasmodium Falciparum Malaria

Further study details as provided by Albert Schweitzer Hospital, Netherlands:

Primary Outcome Measures:
  • Proportion of cured patients by day 28

Secondary Outcome Measures:
  • Proportion of gametocytes carriers during the hospitalisation period and on days 7, 14, 21, and 28
  • Parasite clearance time
  • Fever clearance time
  • Assessment of adverse events during the study period

Estimated Enrollment: 50
Study Start Date: April 2003
Estimated Study Completion Date: February 2004
Detailed Description:

One main concern of clinicians in malaria endemic areas is to find a simple malaria treatment with short treatment duration. The concept of combination therapy, which may reduce treatment duration and delay the spread of drug resistance in addition to an increase in efficacy, has been therefore introduced.

In contrast to the outpatient treatment of malaria where emergence of resistance has lead to new drugs policies, the treatment of hospitalised malaria cases remains, in many endemic countries, intravenous quinine for 7 days. The efficacy of this regimen is well established throughout Africa. The effectiveness of the quinine treatment may be considerably lower because of discontinuation of treatment due to early discharge, the occurrence of side effects or because of the fact that patients feel better and stop the treatment. Therefore, sulfadoxine-pyrimethamine (SP) is often added at discharge. This regimen has been shown to be effective. But in Africa, where the practice seems widespread, it has been assessed in only two trials.

Since resistance of Plasmodium falciparum to SP is increasing rapidly in Africa and there is evidence that SP monotherapy induce gametocytaemia, we hypothesize that the combination quinine/SP increases SP efficacy and prevents induction of gametocytaemia. In addition, since the use of the full course of quinine therapy may be hampered by many factors (hospital cost, hospitalisation duration, availability of beds, compliance and side effects), the addition of the long acting SP to complete a short course of quinine treatment may prevent recrudescence or reinfection and may increase effectiveness of malaria treatment and reduce postdischarge morbidity.

The efficacy and safety of the short course of intravenous quinine (3-day treatment) plus a single dose of oral SP for the treatment of falciparum malaria was investigated.

  Eligibility

Ages Eligible for Study:   2 Years to 7 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Uncomplicated falciparum malaria
  • Asexual parasitaemia between 20,000 and 200,000/µL
  • No mixed plasmodial infection
  • Fever with temperature above 38 °C or history of fever during the preceding 24 hours
  • No effective anti-malarial treatment for the present attack
  • Informed consent

Exclusion Criteria:

  • Haemoglobin < 7 g/dL
  • Packed-cell volume < 20%
  • White cell count > 16,000/µL
  • Platelet count < 40,000/µL
  • Schizontaemia > 50/µL
  • Impaired consciousness
  • Convulsions or history of convulsions
  • Concomitant diseases masking assessment of response
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00167739

Locations
Gabon, Moyen Ogooué
Medical Research Unit, Lambaréné
Lambaréné, Moyen Ogooué, Gabon, B.P. 118
Sponsors and Collaborators
Albert Schweitzer Hospital, Netherlands
Medical Research Unit, Lambaréné
Investigators
Principal Investigator: Michel A. Missinou, PhD Medical Research Unit, Lambaréné
  More Information

General information on malaria at the website of the Malaria Foundation International  This link exits the ClinicalTrials.gov site
Homepage of the Medical Research unit, Lambarene  This link exits the ClinicalTrials.gov site

Publications:
Kremsner PG, Winkler S, Brandts C, Neifer S, Bienzle U, Graninger W. Clindamycin in combination with chloroquine or quinine is an effective therapy for uncomplicated Plasmodium falciparum malaria in children from Gabon. J Infect Dis. 1994 Feb;169(2):467-70.
Alloueche A, Bailey W, Barton S, Bwika J, Chimpeni P, Falade CO, Fehintola FA, Horton J, Jaffar S, Kanyok T, Kremsner PG, Kublin JG, Lang T, Missinou MA, Mkandala C, Oduola AM, Premji Z, Robertson L, Sowunmi A, Ward SA, Winstanley PA. Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: double-blind randomised controlled trial. Lancet. 2004 Jun 5;363(9424):1843-8.
Bousema JT, Gouagna LC, Meutstege AM, Okech BE, Akim NI, Githure JI, Beier JC, Sauerwein RW. Treatment failure of pyrimethamine-sulphadoxine and induction of Plasmodium falciparum gametocytaemia in children in western Kenya. Trop Med Int Health. 2003 May;8(5):427-30.
Kremsner, P. G., Krishna, S. (2004). Antimalarial combinations. Lancet 364, 285-94
Athan E, Durrheim DN, Barnes K, Mngomezulu NM, Mabuza A, Govere J. Effectiveness of short-course quinine and single-dose sulfadoxine-pyrimethamine in the treatment of Plasmodium falciparum malaria in Mpumalanga Province, South Africa. S Afr Med J. 2001 Jul;91(7):592-4.
Rahman MR, Paul DC, Rashid M, Ghosh A, Bangali AM, Jalil MA, Faiz MA. A randomized controlled trial on the efficacy of alternative treatment regimens for uncomplicated falciparum malaria in a multidrug-resistant falciparum area of Bangladesh--narrowing the options for the National Malaria Control Programme? Trans R Soc Trop Med Hyg. 2001 Nov-Dec;95(6):661-7.
Ogutu BR, Nzila AM, Ochong E, Mithwani S, Wamola B, Olola CH, Lowe B, Kokwaro GO, Marsh K, Newton CR. The role of sequential administration of sulphadoxine/pyrimethamine following quinine in the treatment of severe falciparum malaria in children. Trop Med Int Health. 2005 May;10(5):484-8.
Deloron P, Mayombo J, Le Cardinal A, Mezui-Me-Ndong J, Bruzi-Baert C, Lekoulou F, Elissa N. Sulfadoxine-pyrimethamine for the treatment of Plasmodium falciparum malaria in Gabonese children. Trans R Soc Trop Med Hyg. 2000 Mar-Apr;94(2):188-90.
Hall AP, Doberstyn EB, Mettaprakong V, Sonkom P. Falciparum malaria cured by quinine followed by sulfadoxine-pyrimethamine. Br Med J. 1975 Apr 5;2(5961):15-7.
Hall AP, Doberstyn EB, Karnchanachetanee C, Samransamruajkit S, Laixuthai B, Pearlman EJ, Lampe RM, Miller CF, Phintuyothin P. Sequential treatment with quinine and mefloquine or quinine and pyrimethamine-sulfadoxine for falciparum malaria. Br Med J. 1977 Jun 25;1(6077):1626-8.
de Souza JM, Sheth UK, de Oliveira RM, Roulet H, de Souza SD. An open, randomized, phase III clinical trial of mefloquine and of quinine plus sulfadoxine-pyrimethamine in the treatment of symptomatic falciparum malaria in Brazil. Bull World Health Organ. 1985;63(3):603-9. No abstract available.

Study ID Numbers: 04/2003/Q/SP
Study First Received: September 11, 2005
Last Updated: September 19, 2005
ClinicalTrials.gov Identifier: NCT00167739  
Health Authority: Gabon: Ministry of Research

Keywords provided by Albert Schweitzer Hospital, Netherlands:
Malaria
Quinine
Sulfadoxine-pyrimethamine
Gabon

Study placed in the following topic categories:
Folic Acid
Pyrimethamine
Protozoan Infections
Sulfadoxine-pyrimethamine
Quinine
Parasitic Diseases
Malaria
Sulfadoxine
Malaria, Falciparum

Additional relevant MeSH terms:
Anti-Infective Agents
Antiprotozoal Agents
Molecular Mechanisms of Pharmacological Action
Coccidiosis
Physiological Effects of Drugs
Anti-Infective Agents, Urinary
Enzyme Inhibitors
Neuromuscular Agents
Renal Agents
Folic Acid Antagonists
Pharmacologic Actions
Antimalarials
Antiparasitic Agents
Sensory System Agents
Analgesics, Non-Narcotic
Therapeutic Uses
Muscle Relaxants, Central
Analgesics
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009