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Clinical Trial Details (PDF Generation Date :- Thu, 24 Sep 2020 [Link] GMT)

CTRI Number CTRI/2017/11/010703 [Registered on: 29/11/2017] - Trial Registered Retrospectively

Last Modified On 27/11/2017
Post Graduate Thesis No
Type of Trial Interventional
Type of Study Drug
Study Design Single Arm Trial
Public Title of Study Drug resistance studies of antimalarial medicines.
Scientific Title of Monitoring the therapeutic efficacy of antimalarial medicines across International borders of India.
Study
Secondary IDs if Any Secondary ID Identifier
NIL NIL
Details of Principal Details of Principal Investigator
Investigator or overall
Name Neena Valecha
Trial Coordinator
(multi-center study) Designation Scientist G and Director
Affiliation National Institute of Malaria Research
Address Epidemiological Research Division Room no 105 Sector 8 Dwarka
Epidemiological Research Division Room no 105 Sector 8 Dwarka
West
DELHI
110077
India
Phone 01125307104
Fax 01125307177
Email neenavalecha@[Link]
Details Contact Details Contact Person (Scientific Query)
Person (Scientific
Name Neelima Mishra
Query)
Designation ScientistE
Affiliation National Institute of Malaria Research
Address Epidemiological Research Division Room no 333 Sector 8 Dwarka
Epidemiological Research Division Room no 333 Sector 8 Dwarka
West
DELHI
110077
India
Phone 01125307333
Fax 01125361090
Email [Link]@[Link]
Details Contact Details Contact Person (Public Query)
Person (Public Query)
Name Neena Valecha
Designation Scientist G and Director
Affiliation National Institute of Malaria Research
Address Epidemiological Research Division Room no 105 Sector 8 Dwarka
Epidemiological Research Division Room no 105 Sector 8 Dwarka
West
DELHI
110077
India
Phone 01125307104

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Fax 01125307177
Email neenavalecha@[Link]
Source of Monetary or Source of Monetary or Material Support
Material Support
> World Health Organization Global malaria Programme World Health Organization 20 Av. Appia,
1211 Geneva 27 Switzerland
Primary Sponsor Primary Sponsor Details
Name WHO GMP
Address World Health Organization Global malaria Programme 20 Av. Appia,
1211 Geneva 27 Switzerland
Type of Sponsor Other [WHO Global Malaria Programme]
Details of Secondary Name Address
Sponsor
NA NA
Countries of List of Countries
Recruitment
India
Sites of Study Name of Principal Name of Site Site Address Phone/Fax/Email
Investigator
Dr Horen Doley Sr R D Changlang Medical officer Room 09436925146
Shillong for consultation Out
door patient [Link]@[Link]
Department Miao
Primary Health Centre
Changlang district
Changlang
ARUNACHAL
PRADESH
Mr S Phukan District Lunglei Mizoram Medical officer Room 09435342007
for consultation Out
door patient sphookan7@[Link]
Department Tlabung
Sub divisional Hospital
Lunglei
MIZORAM
Dr Neelima Mishra National Institute of Epidemiology and 01125307333
malaria Research clinical research
division room no 333 [Link]@[Link]
Sector 8 Dwarka m
West
DELHI
Dr Sujoy Sukladas PHC Silachari Medical officer incharge 08730988727
Room for consultation
Out door patient [email protected]
department Silachari om
Primary Health Centre
District Gomati
West Tripura
TRIPURA
Details of Ethics Name of Committee Approval Status Date of Approval Is Independent Ethics
Committee Committee?
Institutional Ethics Approved 06/03/2013 No
Commitee, National
Institute of Malaria
Research, sector 8,
Dwarka New Delhi
Institutional Ethics Approved 06/03/2013 No

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Commitee, National
Institute of Malaria
Research, sector 8,
Dwarka New Delhi
Institutional Ethics Approved 06/03/2013 No
Commitee, National
Institute of Malaria
Research, sector 8,
Dwarka New Delhi
Institutional Ethics Approved 06/03/2013 No
Commitee, National
Institute of Malaria
Research, sector 8,
Dwarka New Delhi
Regulatory Clearance Status Date
Status from DCGI
Not Applicable No Date Specified
Health Condition / Health Type Condition
Problems Studied
Patients Parient suffering from uncomplicated falciparum
malaria
Intervention / Type Name Details
Comparator Agent
Intervention Artemether Lumefantrine Administered as per National
policy of that area
Inclusion Criteria Inclusion Criteria
Age From 1.00 Year(s)
Age To 65.00 Year(s)
Gender Both
Details 1 age between 1 year to 65 years
2 Mono infection with P. falciparum detected by microscopy
3 asexual forms parasitaemia of 1000 to 100000 per microlitre of
blood
4 presence of axillary temperature equal and more than 37 5
Centigrade or history of fever during the past 48 hours
5 ability to swallow oral medication
ability and willingness to comply with the study protocol for the
duration of the study and to comply with the study visit schedule
6 informed consent from the patient or from a parent or guardian in
the case of children

Exclusion Criteria Exclusion Criteria

Details 1 presence of general danger signs in children aged under 5 years or
signs of severe falciparum malaria according to the definitions of
WHO
2 mixed or mono-infection with another Plasmodium species
detected by microscopy
3 presence of severe malnutrition
4 presence of febrile conditions due to diseases other than malaria
eg measles acute lower respiratory tract infection severe diarrhoea
with dehydration or other known underlying chronic or severe
diseases eg cardiac renal and hepatic diseases HIV AID
5 regular medication which may interfere with antimalarial
pharmacokinetics
6 history of hypersensitivity reactions or contraindications to any of
the medicines being tested or used as alternative treatments
7 a positive pregnancy test or breastfeeding
unable to or unwilling to take contraceptives for women of
child-bearing age

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8 Minor girls aged less than 18 years who have achieved menarche

Method of Generating Not Applicable

Random Sequence
Method of Not Applicable
Concealment
Blinding/Masking Not Applicable
Primary Outcome Outcome Timepoints
To assess the efficacy and safety of artemether 42 days
Lumefantrine (AL) for the treatment of
uncomplicated P. falciparum infections in Lunglei
district (Mizoram); Changlang district (Arunachal
Pradesh), Gomati district or Dhalai district
(Tripura) in India.
Secondary Outcome Outcome Timepoints
To determine the polymorphism of molecular 42 days
markers for artemether-lumefantrine resistance
and
To determine the blood concentration of
artemether lumefantrine

Target Sample Size Total Sample Size=255

Sample Size from India=255
Final Enrollment numbers achieved (Total)=225
Final Enrollment numbers achieved (India)=225
Phase of Trial N/A
Date of First 01/05/2014
Enrollment (India)
Date of First No Date Specified
Enrollment (Global)
Estimated Duration of Years=0
Trial Months=9
Days=0
Recruitment Status of Not Applicable
Trial (Global)
Recruitment Status of Completed
Trial (India)
Publication Details None yet
Brief Summary

The emergence and spread of Plasmodium falciparum resistance to

commonly used antimalarial drugs is a major challenge in the control and
in the process of achieving elimination of malaria (Olliaro, 2005; The
malERA Consultative Group on Drugs, 2011). For this reason, the
combination therapies rather than monotherapies have been
recommended for efficient management of malaria. WHO endorsed
artemisinin-based combination therapies (ACTs) have proven to be
extremely effective for management of uncomplicated malaria as a part of
global efforts to control and eliminate malaria worldwide (WHO malaria fact

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sheet, 2013).

National drug policy on malaria in India has recommended the use of

artesunate plus sulphadoxine-pyremethamine (AS+SP) which is the first
line of treatment for uncomplicated falciparum malaria. Till 2011, the
efficacy of AS+SP was found to be above 95% at all the study sites in the
country. However studies conducted during 2012 in North-eastern states
showed high treatment failures to AS+SP in P. falciparum malaria with
PCR corrected cure rates ranging between 75-80% (Mishra et al., 2012,
Mishra et al., 2014). There after artemether-lumefantrine (AL) has been
recommended as the first line antimalarial in North-Eastern region
(NVBDCP, 2014). The present study were undertaken to determine
the therapeutic efficacy and safety of artemether-lumefantrine (AL) for the
treatment of uncomplicated P. falciparum malaria in three states (Tripura,
Mizoram and Arunachal Pradesh) in the north-eastern region of India.

The patients were enrolled in the study during the peak malaria
transmission season of P. falciparum in NE region, from April 2014 to
August 2014. Patients were followed up for 42 days after initiation of
treatment at all the 3 sites participating in the surveillance. The in vivo
therapeutic evaluation demonstrated that AL is well tolerated and highly
efficacious up to 28 days of follow up. The 28-day PCR corrected efficacy
rates were 96.1% in each of the districts of Tripura (Gomati)and Mizoram
(Lunglei). 100% efficacxy was observed in Changlang district, Arunachal
Pradesh. However, the PCR corrected efficacy after 42 days follow up was
88.4% in Gomati district, Tripura; 94.3% in Lunglei district, Mizoram and
100% in Changlang district, Arunachal Pradesh. While the efficacy of
first-line treatment AL at 42 days after treatment has been found to be high
in Arunachal Pradesh and Mizoram, it is below the WHO target efficacy of
90% in Tripura. The use of AL as a first-line treatment at this site warrants
close monitoring.

In addition to clinical efficacy, molecular markers of drug resistance of AL

were analysed in all the samples collected on Day 0 from above three
sites. Single-nucleotide polymorphisms (SNPs) in the pfcrt and pfmdr1

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genes are known to be involved in the development of in vitro and in vivo

resistance to AL (Wongsrichanalai et al., 2002). A high prevalence of pfcrt
76T mutations were observed in Gomati (54.1%), Lunglei (95.2%) and
Changlang district (97.6%). Significant selection of pfmdr1 N86, Y184 and
D1246 at Tripura and Mizoram while 86Y, Y184 and D1246 in Arunachal
Pradesh has been observed after AL treatment in the present study.
Furthermore, we found high rates of two pfmdr1 haplotypes previously
associated with lumefantrine resistance, NYD (75%) and YYD (50%) in
treatment failure samples from Tripura and Mizoram respectively. None of
the 12 isolates from patients who were successfully treated (attained
ACPR) from Tripura, Mizoram and Arunachal Pradesh or 12 recrudescent
samples from Tripura and Mizoram had an amplified pfmdr1 gene.

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