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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
Sponsor:
Collaborators:
World Health Organization
HealthNet TPO
United Nations High Commissioner for Refugees
Malaria Control Program, Directorate of Malaria Control, Pakistan
Information provided by (Responsible Party):
Brian Greenwood, London School of Hygiene and Tropical Medicine

Tracking Information
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
 (submitted: September 8, 2005)
  • Day 7 slide clearance rate (complete clearance of trophozoites) assessed by microscopists who are blind to treatment allocation.
  • Day 28 slide clearance rate without subsequent recrudescence.
  • Day 7 gametocyte prevalence.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2005)
  • Day 14 gametocyte prevalence
  • Fever clearance time
  • cure rate (elimination of parasitaemia without recrudescence).
  • Rate and time of parasite clearance.
  • Rate of resolution of fever.
  • Proportion of gametocyte carriers.
  • Transmissibility of gametocytes through mosquito feeding studies.
  • Tolerability.
  • Molecular characterisation of genetic diversity and resistance before and after treatment.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
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.
Detailed Description

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.

Protocol design:

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:

  • CQ (day1,2,3) + placebo (day 1, 3) vs
  • CQ (day 1,2,3) + PQ (day 1) + placebo (day 3) vs
  • CQ (day 1,2,3) + PQ (day 3) + placebo (day 1) vs
  • CQ (day 1,2,3) + AS (day 1) + placebo (day 3)
  • S/P (day 1) + placebo (day 1) vs
  • S/P (day 1) + AS (day 1) vs
  • S/P (day 1) + PQ (day 1)
  • AQ (day 1,2,3) + placebo (day 1,2,3) vs
  • AQ (day 1,2,3) + AS (day 1,2,3)

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
Masking: Single
Primary Purpose: Treatment
Condition  ICMJE
  • Malaria
  • Falciparum Malaria
  • Vivax Malaria
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 Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 3, 2007)
650
Original Enrollment  ICMJE
 (submitted: September 8, 2005)
1050
Actual Study Completion Date  ICMJE December 2004
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • adults or children > 5 yrs
  • weight > 5 kg
  • monoinfection with P. falciparum or P. vivax
  • history of recent fever
  • consent from patient or parent.

Exclusion Criteria:

  • patients with signs of severe malaria.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
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  
 
Administrative Information
NCT Number  ICMJE NCT00158548
Other Study ID Numbers  ICMJE ITDCVC98
ITDCVV98
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
Collaborators  ICMJE
  • World Health Organization
  • HealthNet TPO
  • United Nations High Commissioner for Refugees
  • Malaria Control Program, Directorate of Malaria Control, Pakistan
Investigators  ICMJE
Principal Investigator: Kate Graham, MSc HealthNet International, Peshawar, Pakistan
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