Chloroquine and Post Malaria Anaemia Study

NCT00473837 | Completed Results

• 1 other identifier: SCC1076
• Study Type: interventional
• Target: 96
• Locations: 0 countries
• Sites: N/A

Brief Summary

The pathogenesis of post-malaria anaemia is multifactorial. Iron supplementation remains the mainstay of management of moderate and severe anaemia; however the management of mild anaemia (Hb 80-110g/l) is problematic as population supplementation studies of children in malaria endemic areas demonstrate adverse effects in children with mild anaemia. We hypothesize that the anti-inflammatory, anti-malarial and anti-macrophageal iron loading effects of chloroquine could make it a useful drug in the management of mild post malaria anaemia. To test this hypothesis, we plan to randomize children (aged 12 months to 6 years) with post malaria anaemia (Hb 70-110g/l) to receive a standard anti-malarial treatment, co-artemether . All children with parasitologic cure after three days on treatment will be randomised to receive either weekly chloroquine or weekly placebo starting from day 10 till day 90. By comparing the curve of haemoglobin change between day 3 and day 30 in the placebo arms of the two groups, we will test the effect of chloroquine vs. ACT treatment on macrophageal iron loading and release in acute clinical malaria. By comparing the haemoglobin change between day 3 and day 90 between the weekly chloroquine arms and the weekly placebo arms we will test the longer-term anti-inflammatory and anti- malarial effects of weekly chloroquine prophylaxis. In addition to the primary endpoint, we plan to assess potential mechanisms of action by determining parasite clearance, peripheral cytokine production and iron flux

Conditions

Malaria Anaemia

Keywords

malaria; anaemia; chloroquine; iron delocalisation; macrophages

Outcome Measures

Primary Outcomes (1)

• Changes in Haemoglobin Concentration From Day 3 Post Treatment of Malaria Episode to Day 90 in the Weekly Chloroquine and Placebo Arms

  90 days

Secondary Outcomes (1)

• Curve of Hb Change Between Day 3 and Day 30 in the Two Placebo Arms; Changes in Markers of Iron Status, Measures of Inflammation, and Hb Response Between Day 3 and Day 30, and Between Day 3 and Day 90

  90 days

Study Arms (2)

Treatment

ACTIVE COMPARATOR

Subjects initially treated with Co-arthemeter, and then continued on weekly chloroquine till day 90

Drug: Chloroquine

Control

PLACEBO COMPARATOR

Subjects initially treated with Co-arthemeter, and then continued on weekly placebo till day 90

Drug: Placebo

Interventions

Chloroquine DRUG

This is an orange syrup in a 60ml amber coloured glass bottle containing 50mg of chloroquine base per 5mls as the chloroquine phosphate. The syrup was manufactured by Medreich Sterilab Ltd, Avalahalli, Bangalore, India. Chloroquine: weekly treatment of 7.5mg/kg for 90 days

Treatment

Placebo DRUG

The placebo is an orange syrup in a 60ml amber coloured glass bottle containing sucrose syrup base. The syrup was prepared by the Pharmacy department of the Royal Victorial Teaching Hospital and Atlantic Pharmaceuticals Limited, Banjul

Control

Eligibility Criteria

• Age: 12 Months - 72 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Children aged 12 months to 6 years; and
• History of fever in the preceding 48 hours or a measured temperature \> 37.5oC plus asexual forms of P. falciparum in the peripheral blood film of 500/μl or above; and
• Hb \<110g/l and \>69g/l (Our choice of the upper limit of moderate anaemia (70 - 79g/l) is to enable us assess the response to our interventions of severer forms of anaemia while at the same time reducing the risk of adverse events which might occur with lower levels of Hb).

You may not qualify if:

• Refusal of parent or guardian to give consent to the child's participation in the study
• Inability of the subjects to take oral medications
• Presence of features of severe malaria as defined by WHO50, with the exception of anaemia and parasite density
• Children who have urgent need for blood transfusion as indicated by the presence of tachypnoea, tachycardia \& gallop rhythm, tender hepatomegaly
• Children with known haemoglobinopathy
• Children with a weight for height Z score below -3SD of WHO/NCHS standard
• Enrolment in another research project

Sponsors & Collaborators

• Medical Research Council Unit, The Gambia: lead

Related Publications (2)

• 1. Weatherall DJ, et al. Br Med Bull 1982;38(2):147-51. 2. Schwartz RS, et al.Blood 1987;69(2):401-7. 4. Looareesuwan S, et al. Acta Trop 1991;48(4):263-70. 5. Abdalla SH, et al. Clin Lab Haematol 1988;10(1):33-40. 6. Jootar S, et al. Clin Lab Haematol 1993;15(2):87-92. 7. Jason J, et al. Clin Immunol 2001;100(2):208-18. 8. Clark IA, et al. Br J Haematol 1988;70(1):99-103. 9. Biemba G, et al. Trop Med Int Health 2000;5(4):256-62. 10. Othoro C, et al, J Infect Dis 1999;179(1):279-82. 11. Luty AJ, et al. Infect Immun 2000;68(7):3909-15. 12. Camacho LH, et al. Ann Trop Med Parasitol 1998;92(5):525-37. 13. Kwiatkowski D, et al. Clin Exp Immunol 1989;77(3):361-6. 15. Wenisch C, et al. Clin Immunol Immunopathol 1995;74(1):115-7. 17. Helleberg M, et al. Malar J 2005;4(1):56. 18. Knutson M, et al, Crit Rev Biochem Mol Biol 2003;38(1):61-88. 23. Abdalla S, et al. Br J Haematol 1980;46(2):171-83. 24. Bojang KA, et al. Trans R Soc Trop Med Hyg 1997;91(5):557-61. 30. Moore HP, et al. Nature 1983;302(5907):434-6. 31. Agarwal SL, et al, Arch Int Pharmacodyn Ther 1963;143:401-7. 32. Ayitey-Smith E, et al. J Pharm Pharmacol 1974;26(3):208-9. 33. Moss RB. Chest 1995;107(3):817-25. 34. Lancz GJ, et al. Proc Soc Exp Biol Med 1971;136(4):1289-93. 35. Tsai WP, et al. AIDS Res Hum Retroviruses 1990;6(4):481-9. 36. Boelaert JR, et al. J Acquir Immune Defic Syndr 2001;26(3):300-1. 37. Neale ML, et al.Immunology 1988;64(1):81-5. 39. Cash JM, et al. N Engl J Med 1994;330(19):1368-75. 40. Legssyer R, et al. Biochem Pharmacol 1999;57(8):907-11. 41. Salihu HM, et al. Trop Med Int Health 2002;7(1):29-34. 42. Cot M, le Hesran JY, et al. Ann Trop Med Parasitol 1998;92(1):37-43.

  BACKGROUND

• Cox SE, Nweneka CV, Doherty CP, Fulford AJ, Moore SE, Prentice AM. Randomised controlled trial of weekly chloroquine to re-establish normal erythron iron flux and haemoglobin recovery in postmalarial anaemia. BMJ Open. 2013 Jul 4;3(7):e002666. doi: 10.1136/bmjopen-2013-002666. Print 2013.

  PMID: 23833120 DERIVED

Related Links

• Medical Research Council Laboratories, The Gambia web site

MeSH Terms

Conditions

Malaria; Anemia

Interventions

Chloroquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Mrs Vivat Thomas-Njie
• Organization: Medical Research Council Unit, The Gambia

vthomas@mrc.gm

+220-4495442/6

Study Officials

• Chidi V Nweneka, MSc.

  Medical Research Council Unit, The Gambia

  PRINCIPAL INVESTIGATOR

• Sophie Moore, PhD

  Medical Research Council Unit, The Gambia

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2007
• First Posted: May 16, 2007
• Study Start: July 1, 2007
• Primary Completion: February 1, 2009
• Study Completion: December 1, 2009
• Last Updated: October 13, 2014
• Results First Posted: October 13, 2014

Record last verified: 2014-10