Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00158548
Other study ID # ITDCVC98
Secondary ID ITDCVV98
Status Completed
Phase Phase 3
First received September 8, 2005
Last updated January 11, 2017
Start date June 2001
Est. completion date December 2004

Study information

Verified date January 2017
Source London School of Hygiene and Tropical Medicine
Contact n/a
Is FDA regulated No
Health authority Pakistan: Ministry of HealthPakistan: Research Ethics Committee
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 650
Est. completion date December 2004
Est. primary completion date
Accepts healthy volunteers No
Gender All
Age group 5 Years to 70 Years
Eligibility 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind, Primary Purpose: Treatment


Intervention

Drug:
SP, chloroquine, amodiaquine, primaquine, artesunate


Locations

Country Name City State
Pakistan HealthNet International Peshawar

Sponsors (5)

Lead Sponsor Collaborator
London School of Hygiene and Tropical Medicine HealthNet TPO, Pakistan Directorate of Malaria Control, United Nations High Commissioner for Refugees, World Health Organization

Country where clinical trial is conducted

Pakistan, 

Outcome

Type Measure Description Time frame Safety issue
Primary Day 7 slide clearance rate (complete clearance of trophozoites) assessed by microscopists who are blind to treatment allocation.
Primary Day 28 slide clearance rate without subsequent recrudescence.
Primary Day 7 gametocyte prevalence.
Secondary Day 14 gametocyte prevalence
Secondary Fever clearance time
Secondary cure rate (elimination of parasitaemia without recrudescence).
Secondary Rate and time of parasite clearance.
Secondary Rate of resolution of fever.
Secondary Proportion of gametocyte carriers.
Secondary Transmissibility of gametocytes through mosquito feeding studies.
Secondary Tolerability.
Secondary Molecular characterisation of genetic diversity and resistance before and after treatment.
See also
  Status Clinical Trial Phase
Completed NCT04601714 - Baseline Cohort Malaria Morbidity Study
Withdrawn NCT04020653 - A Study to Assess the Safety and Efficacy of 5-aminolevulinic Acid Hydrochloride (5-ALA HCl) and Sodium Ferrous Citrate (SFC) Added on Artemisinin-based Combination Therapy (ACT) in Adult Patients With Uncomplicated Malaria Phase 2
Terminated NCT04368910 - Safety and Efficacy of Pyronaridine Artesunate Vs Chloroquine in Children and Adult Patients With Acute Vivax Malaria Phase 3
Completed NCT03641339 - Defining Skin Immunity of a Bite of Key Insect Vectors in Humans N/A
Completed NCT02544048 - Markers of T Cell Suppression: Antimalarial Treatment and Vaccine Responses in Healthy Malian Adults
Completed NCT00527163 - Role of Nitric Oxide in Malaria
Not yet recruiting NCT05934318 - L-ArGinine to pRevent advErse prEgnancy Outcomes (AGREE) N/A
Active, not recruiting NCT04704674 - Community Dynamics of Malaria Transmission in Humans and Mosquitoes in Fleh-la and Marshansue, Salala District, Bong County, Liberia
Completed NCT03276962 - Efficacy, Safety and Immunogenicity Study of GSK Biologicals' Candidate Malaria Vaccine (SB257049) Evaluating Schedules With or Without Fractional Doses, Early Dose 4 and Yearly Doses, in Children 5-17 Months of Age Phase 2
Completed NCT04966871 - Safety, Tolerability and Efficacy of PfSPZ Vaccine Against Heterologous CHMI in US Malaria naïve Adults Phase 1
Completed NCT00289185 - Study of Safety, Immunogenicity and Efficacy of a Candidate Malaria Vaccine in Tanzanian Infants Phase 2
Recruiting NCT03937817 - Collection of Human Biospecimens for Basic and Clinical Research Into Globin Variants
Active, not recruiting NCT06153862 - Africa Ready Malaria Screening N/A
Completed NCT04545905 - Antenatal Care as a Platform for Malaria Surveillance: Utilizing Community Prevalence Measures From the New Nets Project to Validate ANC Surveillance of Malaria in Burkina Faso
Recruiting NCT06278181 - Diabetes, Metabolic Syndrome and Risk of Malaria in Cameroon
Completed NCT02793622 - Prevention of Malaria in HIV-uninfected Pregnant Women and Infants Phase 3
Completed NCT02909712 - Cardiac Safety of Dihydroartemisinin-Piperaquine Amongst Pregnant Women in Tanzania Phase 2
Withdrawn NCT02793388 - A Trial on Supervised Primaquine Use in Ethiopia Phase 4
Withdrawn NCT02793414 - Diagnostic Utility of Volatile Organic Compounds in Human Breath for Acute Clinical Malaria in Ethiopia
Completed NCT02315690 - Evaluation of Reactive Focal Mass Drug Administration for Malaria Elimination in Swaziland Phase 3