ACT With Chloroquine, Amodiaquine & Sulphadoxine-pyrimethamine in Pakistan
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|ClinicalTrials.gov Identifier: NCT00158548|
Recruitment Status : Completed
First Posted : September 12, 2005
Last Update Posted : January 12, 2017
|First Submitted Date ICMJE||September 8, 2005|
|First Posted Date ICMJE||September 12, 2005|
|Last Update Posted Date||January 12, 2017|
|Study Start Date ICMJE||June 2001|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||ACT With Chloroquine, Amodiaquine & Sulphadoxine-pyrimethamine in Pakistan|
|Official Title ICMJE||Studies on Adding Artesunate to Existing Antimalarial Therapies With Chloroquine, Amodiaquine & Sulphadoxine-pyrimethamine in Pakistan|
|Brief Summary||Chloroquine resistant falciparum malaria in Pakistan is prevalent in every malarious area examined. Resistance to the favoured second-line treatment, sulphadoxine-pyrimethamine S/P is rising fast. To avert a repetition of the resistance catastrophe that occurred in SE Asia it is critical to preserve the effective life of SP by using it in combination with artesunate. Efficacy of ACT with artesunate in combination with chloroquine, SP or amodiaquine for treatment of malaria (falciparum or vivax) will be examined in malaria patients in Pakistan.|
The incidence of falciparum malaria in Pakistan has risen 6-fold over the last 15 years and chloroquine resistance is prevalent in every malarious area examined. Chloroquine's position as first line treatment must be reconsidered. Resistance to the favoured second-line treatment, sulphadoxine-pyrimethamine SP, is 10% and rising fast. It is critical to preserve the effective life of SP by using it in combination with a non-related fast-acting antimalarial such as artesunate (AS). It is conceivable that use of AS in combination with chloroquine itself might even recover the latter's effectiveness and restrain the selection of stronger levels of chloroquine resistance. To determine the tolerability and efficacy of AS combination therapy in the subcontinent, randomized controlled trials will be conducted by HealthNet International and government staff, with technical support from LSHTM, in Afghan refugee camps in Pakistan against the current therapies of chloroquine, amodiaquine and SP. Current policy is to use primaquine(PQ) as the gametocytocidal drug with CQ or SP. It is not clear whether this has any value in the face of high levels of CQ resistance. The efficacy of PQ in combination with CQ or SP will be examined in individual randomised trial in comparison with CQ or SP alone.
In the past, treatment of falciparum and vivax malaria was with chloroquine. With development of drug resistance treatment of the two species is diverging and this places higher priority on accurate differential diagnosis which cannot always be met at peripheral health posts. There may be advantage in harmonising treatment of the two species with ACT. Thus the current treatment for vivax, chloroquine, shall be compared with that of ACT with artesunate and SP, the likely ACT to be adopted for falciparum malaria.
Randomised, single-blind, controlled trials comparing for falciparum malaria (1) artesunate (AS) and chloroquine (CQ), vs CQ alone, vs CQ and primaquine (PQ); (2) AS and sulphadoxine-pyrimethamine (SP), vs SP alone, vs SP and PQ; (3) AS and amodiaquine (AQ), vs AQ alone.
Randomised, single-blind, controlled trial comparing for vivax malaria: AS and sulphadoxine-pyrimethamine (SP), vs CQ alone.
Patients will be randomly assigned to one of the following treatment groups:
To determine the viability and transmissibility of any gametocytes (and also to detect sub-patent gametocytaemias) still present after treatment it is also proposed to carry out mosquito feeding studies directly on patients on the 7th day after the start of combination therapy with either CQ, CQ+AS, CQ+PQ., SP, SP+AS, SP+PQ and to incubate any midgut infections to the oocyst stage. To determine the genetic consequences of any selection from the different drugs (i.e. CQ, AS, or PQ), the mosquito midgut infections would be preserved for further genetic studies in UK, as would blood samples taken from initial and recrudescent infections.
To improve our understanding of the genetic basis of drug resistance we will genotype parasites from blood samples of patients with treatment failure in this study. Blood samples of 20 patients from each arm of the study who had parasitological treatment failure will be selected randomly, together with midgut infections, and analysed for genetic markers of resistance to chloroquine and sulphadoxine/pyrimethamine. These will be compared with genotypes of pre-treatment infections.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Intervention ICMJE||Drug: SP, chloroquine, amodiaquine, primaquine, artesunate|
|Study Arms ICMJE||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Enrollment ICMJE
|Actual Study Completion Date ICMJE||December 2004|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages ICMJE||5 Years to 70 Years (Child, Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Pakistan|
|Removed Location Countries|
|NCT Number ICMJE||NCT00158548|
|Other Study ID Numbers ICMJE||ITDCVC98
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Brian Greenwood, London School of Hygiene and Tropical Medicine|
|Study Sponsor ICMJE||London School of Hygiene and Tropical Medicine|
|PRS Account||London School of Hygiene and Tropical Medicine|
|Verification Date||January 2017|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP