Evaluation of the Efficacy of Artemisinin Combination Therapy in Kenya

NCT01899820 | Unknown Phase 3 DMC

• 2 other identifiers: KEMRI_CT_2013/0017SSC 2276
• Study Type: interventional
• Target: 2,100
• Locations: 1 country
• Sites: 7

Brief Summary

Artemisinin-based combination therapies (ACTs) are recommended for use against uncomplicated malaria in areas of multi-drug resistant malaria. The Ministry of Health, Division of Malaria Control (DOMC) rolled out the use of artemether-lumefantrine as the first line treatment for uncomplicated malaria in 2006.The development of the ACTs and its derivatives are the most rapidly acting of all the current antimalarial drugs and recognition of their potential role as a component of combination therapy have led to several large trials aimed at assessing different combinations of existing drugs, and to the specific development of new combination drugs. This proposal aims to (1) evaluate the efficacy of artemisinin-based anti-malaria combination drugs in different sites across Kenya (2) elucidate the markers of resistance to ACTs through molecular genetics and in this process further strengthen capacity in the proposed study sites as well as improve links between research and control ultimately to influence malaria treatment policy and practice. Five groups in East Africa will conduct a multi-centre, randomised, two arm trial to assess the efficacy of dihydroartemisin-piperaquine with artemether-lumefantrine as the comparative drug. The network will determine antimalarial drug efficacy using standardised protocols and collate clinical responses and adverse events. Molecular markers to artemisinin resistance will be investigated by molecular sequencing and comparison of parasite profiles in drug failure cases. Recrudescence or re-infections will be differentiated by analysis of the MSP1, MSP2 and GLURP genes and assess transmission dynamics post treatment. Data from these studies will be captured into a database developed by the network. The latter offers several advantages including

• Working towards the standardization of methodologies and common protocols as a way of comparing data across sites
• Pulling together datasets and conduct a multi-centre analysis
• Sharing and coordinating quality assurance mechanisms

Conditions

Malaria

Outcome Measures

Primary Outcomes (1)

• The primary endpoint will be the PCR-corrected and parasitological response (PCR corrected ACPR) at days 28 and 42. Change in this outcome measure will be assessed.

  ACPR is defined as the absence of parasitaemia on day 42 irrespective of the temperature without previously meeting any of the criteria of early treatment failure or late clinical or parasitological failure. Patients with late asexual parasite reappearance will be considered ACPR if the CR analyses shows a new infection rather than a recrudescence (through PCR genotyping). The total treatment failure is defined according to the WHO criteria as the sum of early and late treatment failures.

  Day 28 and day 42

Secondary Outcomes (12)

• Crude (PCR uncorrected) ACPR ratio at day 28 (PCR uncorrected ACPR)

  Day 28

• Cure ratios at day 28, 42, (PCR corrected and PCR uncorrected). Change in this outcome measure will be assessed.

  Day 28 and day 42

• Fever Clearance Time (FCT)

  0 to 48 hours

• Asexual parasite clearance time (PCT)

  Day 0 to day 28, upto day 42

• Gametocyte carrier rates and geometric mean densities (excluding negatives) will be compared on days 7, 14, 28 and 42. Change in this outcome measure will be assessed.

  Day 7, 14, 28 and 42

Study Arms (2)

Artemether lumefantrine

ACTIVE COMPARATOR

Tablets, 1-4 tablets (weight calculated dose), BD, at hr 0, 8, 24, 36, 48 and 60.

Drug: Artemether lumefantrine

Dihydroartemisinin piperaquine

EXPERIMENTAL

Tablets, 2 paediatric tablets/1 adult tablet, OD, every 24 hours for 48 hours

Drug: Dihydroartemisinin piperaquine

Interventions

Artemether lumefantrine DRUG

Artemether 20mg Lumefantrine 120mg

Also known as: Coartem

Artemether lumefantrine

Dihydroartemisinin piperaquine DRUG

Dihydroartemisinin 20mg Piperaquine 160mg

Also known as: Duocortexin

Dihydroartemisinin piperaquine

Eligibility Criteria

• Age: 6 Months - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age between 6 months - 5 years (in high endemic areas); 6 months to 10 years (in low endemic areas) inclusive.
• Presence of axillary temperature \> 37.5oC or rectal / tympanic temp \> 38.0oC, or history of fever in the last 24 hours.
• Monoinfection with Plasmodium falciparum with parasitaemia, asexual parasitemia between 2,000 - 200,000 p/µl (in areas of high transmission); 1,000-100,000p/ µl (in areas of low to moderate malaria transmission)
• Ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; and
• Signed informed consent form by the parents or legal guardian.

You may not qualify if:

• Presence of clinical danger signs: not able to drink or breast-feed, vomiting (\>twice in 24 hours), recent history of convulsions (\>1 in 24h), unconscious state, unable to sit or stand;
• Mixed or mono-infection with another Plasmodium species detected by microscopy;
• Presence of co-morbid infection (e.g. acute lower respiratory tract infection, severe diarrhoea with dehydration, Severe Anaemia) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases,Epilepsy, HIV/AIDS);
• History of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s).

Sponsors & Collaborators

• Sabah Ahmed Omar: lead
• World Bank: collaborator
• Kenya Medical Research Institute: collaborator

Study Sites (7)

Busia district hospitals

Busia, Busia County, Kenya

Location

Kisii district hospitals

Kisii, Kisii County, Kenya

Location

Kitale district hospitals

Kitale, Kitale, Kenya

Location

Msambweni sub-district hospital

Msambweni, Kwale County, Kenya

Location

Machakos district hospital

Machakos, Machakos County, Kenya

Location

Malindi district hospitals

Malindi, Malindi, Kenya

Location

Nyando district hospital

Nyando, Nyando, Kenya

Location

MeSH Terms

Conditions

Malaria

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Sabah A Omar, PhD

  KEMRI CGMR-C

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Centre Director of KEMRI CGMR-C and Study Principal Investigator

Study Record Dates

• First Submitted: April 17, 2013
• First Posted: July 15, 2013
• Study Start: April 1, 2013
• Primary Completion: June 1, 2014
• Study Completion: July 1, 2015
• Last Updated: October 8, 2013

Record last verified: 2013-10

Locations

KE (7)