Investigating resistance to DHA-PIP for the treatment of Plasmodium falciparum malaria and chloroquine for the treatment of Plasmodium vivax malaria in Yunnan, China
| ISRCTN | ISRCTN11775446 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11775446 |
- Submission date
- 13/04/2020
- Registration date
- 17/04/2020
- Last edited
- 13/11/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
Malaria is caused by infection of blood cells with Plasmodium parasites. People with malaria feel unwell and typically have fever, tiredness, vomiting, and headaches. Malaria can lead to death, and if not treated, it can cause repeated bouts of illness. The World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) for the initial treatment of malaria with no complications caused by Plasmodium falciparum. Chloroquine is recommended for treatment of Plasmodium vivax malaria. However, there have been reports of resistance of the parasite infection to treatment with these drugs in countries such as Myanmar, Thailand, Vietnam and Cambodia that border China. This study aims to investigate how effective these malaria treatments are in Yunnan, a province of China in the south-east of the country that borders Myanmar, Laos and Vietnam.
Who can participate?
People aged 6 months to 60 years who have malaria and are infected with Plasmodium falciparum or Plasmodium vivax, but not both.
What does the study involve?
People will receive the usual treatment for each type of parasite in the health centre for 3 days. Those with Plasmodium falciparum infection will receive DHA-PIP (dihydroartemisinin and piperaquine) and will be followed up for 42 days. Those with Plasmodium vivax infection will receive chloroquine and will be followed up for 28 days. The follow-up will include blood tests to investigate whether the parasite has been fully cleared from the blood.
What are the possible benefits and risks of participating?
The medicines may have some minor side effects. It is also possible that they may cause some problems that are unexpected; however, the researchers and healthcare staff will follow the participants closely and keep track of these effects, if they arise, and of any other problems. Participants will be given a telephone number to call if they notice anything out of the ordinary or if they have concerns or questions. They can also come to the health facility at any time and ask to see the doctor or to speak with a doctor on the telephone. If they experience side-effects, the researchers may use some other medicine, free of charge, to help to reduce the symptoms or reactions, or they may stop one or more of the medicines. If this is necessary, it will be discussed together with participants. Participants will always be consulted before any changes are made to the treatment.
Where is the study run from?
The National Institute of Parasitic Disease (China)
When is the study starting and how long is it expected to run for?
June 2012 to December 2016
Who is funding the study?
The WHO, the National Natural Science Foundation of China and the Global Fund to Fight AIDS, Tuberculosis and Malaria
Who is the main contact?
Mei Li, li_mei76@163.com
Contact information
Scientific
National Institute of Parasitic Disease
Chinese Center for Disease Control and Prevention
207 Ruijin Er Rd
Shanghai
200025
China
| Phone | +86-21-64377008 |
|---|---|
| limei@nipd.chinacdc.cn |
Scientific
Yunnan Institute of Parasitic Diseases
6 West Yuan Road
Simao City
Yunnan Province
Pu'er
665000
China
| liubible@126.com |
Scientific
Office of the WHO Representative to Thailand
Bangkok
10400
Thailand
| bustosm@who.int |
Study information
| Study design | Observational surveillance study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross sectional study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | No participant information sheet available. |
| Scientific title | Efficacy and safety of DHA-PIP for the treatment of uncomplicated Plasmodium falciparum malaria and chloroquine for the treatment of Plasmodium vivax malaria in Yunnan, China |
| Study hypothesis | Based on the fact that "suspected resistance" and "confirmed resistance" of falciparum malaria to ACT arose and spread in South-east Asian locations, such as Myanmar, Thailand, Viet Nam and Cambodia, it is important to continuously monitor the efficacy of DHA-PIP in these sites and neighbouring areas and to monitor its distribution or spread in Yunnan. Additionally, more studies are needed to confirm the relationship of some K13 mutations with anti-malaria drug resistance. |
| Ethics approval(s) | 1. Approved 19/06/2012, WHO Office for the Western Pacific Ethics Review Committee (no address, telephone number or email), ref: 2012.11.CHN.04.MVP 2. Approved 06/09/2013, Chinese Center for Disease Control and Prevention Ethical Review Committee (155 Changbai Road, Changping District, Beijing, China 102206; +86-10-58900001; chenchunming@chinacdc.cn), no reference number 3. Approved 21/03/2016, National Institute of Parasitic Diseases Ethical Review Committee (207 Ruijin Er Road, Shanghai, China 200025; +86 21 64377008; lizhen@nipd.chinacdc.cn), no reference number |
| Condition | Uncomplicated Plasmodium falciparum and vivax malaria |
| Intervention | This surveillance study is a one-arm prospective evaluation of clinical and parasitological responses to directly observed treatment for uncomplicated malaria. People with uncomplicated falciparum and vivax malaria who meet the study inclusion criteria will be enrolled, treated on-site with 3-day DHA-PIP (dihydroartemisinin + piperaquine) and chloroquine, and monitored for 42 and 28 days, respectively. The follow-up will consist of a fixed schedule of check-up visits and corresponding clinical and laboratory examinations. On the basis of the results of these assessments, the patients will be classified as having therapeutic failure (early or late) or an adequate response. The proportion of patients experiencing therapeutic failure during the follow-up period will be used to estimate the efficacy of the study drug(s). PCR analysis will be used to distinguish between a true recrudescence due to treatment failure and episodes of re-infection. Treatment(s) and follow-up: Patients infected with P. falciparum will be treated with DHA-PIP at a dose of 2 mg/kg/day DHA and 16 mg/kg/day PIP for 3 days. Patients with P. vivax infection will be treated with chloroquine at a total dose of 25 mg base/kg body weight over 3 days. Clinical and parasitological parameters will be monitored over a 42- or 28-day follow-up period to evaluate drug efficacy. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Dihydroartemisinin + piperaquine, chloroquine |
| Primary outcome measure | 1. Early treatment failure, defined as any one of the following: 1.1. Danger signs or severe malaria on day 1, 2 or 3 in the presence of parasitaemia 1.2. Parasitaemia on day 2 higher than on day 0, irrespective of axillary temperature 1.3. Parasitaemia on day 3 with axillary temperature ≥37.5ºC 1.4. Parasitaemia on day 3 ≥25% of count on day 0 2. Late clinical failure, defined as any one of the following: 2.1. Danger signs or severe malaria in the presence of parasitaemia on any day between day 4 and day 28 for P. vivax patients and day 42 for P. falciparum patients in patients who did not previously meet any of the criteria of early treatment failure 2.2. Presence of parasitaemia on any day between day 4 and day 28 for P. vivax patients and day 42 for P. falciparum patients with axillary temperature ≥37.5ºC (or history of fever) in patients who did not previously meet any of the criteria of early treatment failure 3. Late parasitological failure, defined as presence of parasitaemia on any day between day 7 and day 28 for P. vivax patients and day 42 for P. falciparum patients with axillary temperature <37.5ºC in patients who did not previously meet any of the criteria of early treatment failure or late clinical failure 4. Adequate clinical and parasitological response, defined as absence of parasitaemia on day 28 for P. vivax patients and day 42 for P. falciparum patients, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure Recrudescence will be distinguished from re-infection by polymerase chain reaction (PCR) analysis. |
| Secondary outcome measures | The frequency and nature of adverse events |
| Overall study start date | 10/11/2011 |
| Overall study end date | 28/02/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 6 Months |
| Upper age limit | 60 Years |
| Sex | Both |
| Target number of participants | 110 |
| Participant inclusion criteria | 1. Age between 6 months and 60 years 2. Mono-infection with P. falciparum or P. vivax detected by microscopy 3. Mono-infection with P. falciparum detected by microscopy with parasitaemia of 500-100,000/μl asexual forms 4. Mono-infection with P. vivax detected by microscopy with parasitaemia of ≥250/μl asexual forms 5. Axillary or tympanic temperature ≥37.5°C or oral or rectal temperature of ≥38°C or history of fever during the past 24 h 6. Able to swallow oral medication 7. Able and willing to comply with the study protocol for the duration of the study and to comply with the study visit schedule 8. Informed consent from the patient or from a parent or guardian in the case of children aged less than 18 years 9. Informed assent from any minor participant aged from 12 to age of 18 years 10. Consent for pregnancy testing from female of child-bearing potential and from their parent or guardian if under the age of 18 years |
| Participant exclusion criteria | 1. Presence of general danger signs in children aged under 5 years or signs of severe falciparum malaria according to WHO definitions 2. Weight under 5 kg 3. Mixed infection or mono-infection with another Plasmodium species detected by microscopy 4. Presence of severe malnutrition defined as a child aged 6-60 months whose weight-for-height is below –3 z-score, has symmetrical oedema involving at least the feet or has a mid-upper arm circumference < 115 mm) 5. Presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS) 6. Regular medication, which may interfere with antimalarial pharmacokinetics 7. History of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s) 8. Positive pregnancy test or breastfeeding 9. Unable to or unwilling to take pregnancy test or to use contraception for women of child-bearing age and who are sexually active |
| Recruitment start date | 23/04/2012 |
| Recruitment end date | 28/12/2016 |
Locations
Countries of recruitment
- China
Study participating centres
Shanghai
200025
China
Simao district
Pu'er City
665000
China
Sponsor information
Other
WHO/GSC/GPL
Block 3510
Janlan Teknokrat 6
Cyberjaya
63000
Malaysia
| Phone | +86 10 65327189 up to 7192 |
|---|---|
| who.chn@wpro.who.int | |
| Website | http://www.searo.who.int/en/ |
"ROR" |
https://ror.org/02wae9s43 |
Government
83, Shuangqing Road
Haidian District
Beijing
100085
China
| Phone | +86 10-62327195 |
|---|---|
| support@nsfc.gov.cn | |
| Website | http://www.nsfc.gov.cn/publish/portal1/ |
Funders
Funder type
Other
Private sector organisation / International organizations
- Alternative name(s)
- منظمة الصحة العالمية, 世界卫生组织, Всемирная организация здравоохранения, Organisation mondiale de la Santé, Organización Mundial de la Salud, WHO, 世卫组织, ВОЗ, OMS
- Location
- Switzerland
Government organisation / National government
- Alternative name(s)
- Chinese National Science Foundation, Natural Science Foundation of China, National Science Foundation of China, NNSF of China, NSF of China, 国家自然科学基金委员会, National Nature Science Foundation of China, Guójiā Zìrán Kēxué Jījīn Wěiyuánhuì, NSFC, NNSF, NNSFC
- Location
- China
Private sector organisation / International organizations
- Alternative name(s)
- Global Fund, Fonds mondial, The Global Fund to Fight AIDS, Tuberculosis and Malaria, Fonds mondial de lutte contre le sida, la tuberculose et le paludisme, The Global Fund, Le Fonds mondial, GFATM
- Location
- Switzerland
Results and Publications
| Intention to publish date | 30/11/2020 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Both the follow-up results and molecular testing results will be published as soon as they are finished. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Other publications | Genetic analysis of P. falciparum parasites collected from 2012 to 2016 along the China-Myanmar border | 10/11/2023 | 13/11/2023 | Yes | No |
Editorial Notes
13/11/2023: Publication reference added.
15/04/2020: Trial's existence confirmed by the World Health Organization (WHO).
