Clinical trial NCT01828333: Malaria Treatment With Injectable ArteSunate
Official title: Treatment of Severe Malaria - An Operational Comparative Study Between Quinine and Artesunate for the Treatment of Severe Malaria in Hospitals and Health Centers of Kinshasa and Lower Congo
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Severe Malaria
Keywords: Malaria
Severe
Artesunate
Quinine
Democratic Republic of Congo
Lead sponsor: Swiss Tropical & Public Health Institute
Sponsor class: OTHER
Collaborators: name: Medicines for Malaria Venture
First posted: 2013-04-10
Enrollment: 350
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with severe malaria will be enrolled in four hospitals and five health centers located in four health zones of the Democratic Republic of the Congo, three rural and one urban.

Brief summary: The MATIAS study aims to demonstrate through limited scope implementation studies how injectable artesunate may be progressively rolled out nationwide in the Democratic Republic of the Congo as the preferred treatment for severe malaria.

Detailed description: In 2010 the AQUAMAT study demonstrated that the treatment of severe malaria with artesunate in children reduced the case fatality substantially. An overall reduction of 22.5 % of mortality in African children (\< 15 years) was reported using injectable artesunate compared to injectable quinine for treatment of severe malaria caused by Plasmodium falciparum. These results with high quality evidence led to a change in the WHO guidelines for the treatment of severe malaria in 2011. The WHO now recommends intravenous artesunate as the treatment of choice for severe malaria in children and adults. In early 2012 the Programme National de Lutte contre of Paludisme (PNLP) of the DRC with support from the relevant ministry departments decided to follow the WHO guidelines and changed the policy for the treatment of severe malaria in children and adults from injectable quinine to injectable artesunate. However, this process is a complex undertaking, requiring many operational and clinical adaptations. In order to support this process, there is a need for on-site operational information on the process and consequences of the switch from quinine to artesunate. The MATIAS study aims to demonstrate through limited scope implementation studies how injectable artesunate may be progressively rolled out nationwide in the Democratic Republic of the Congo as the preferred treatment for severe malaria.

Eligibility criteria: Inclusion Criteria:

Patients (= 2 months old) admitted to one of the study sites and treated for severe malaria with IV quinine in the first part of the study and patients treated with IV/IM artesunate in the second part of the study will be included. Patients need to fulfill the WHO criteria for severe malaria and must be unable to take oral treatment (WHO, 2010, WHO, 2011). In addition all participants need to give their informed consent

Conditions: Positive rapid diagnostic test (RDT) for Plasmodium falciparum HRP2 or lactate dehydrogenase and/or a positive blood slide (thick smear). Patient will be considered to be positive if one of the two tests is positive. In case of negative result of both tests, the patient will not be enrolled in the study and will receive care according to the usual routine practice in the hospital/health center in question.

Definition of severe malaria according to WHO (WHO, 2010): In a patient with P. falciparum asexual parasitaemia and no other obvious cause for the symptoms, the presence of one or more of the following clinical or laboratory features classifies the patient as suffering from severe malaria:

Clinical features (hospitals and health centers):

* impaired consciousness or unrousable coma
* prostration, i.e. generalized weakness so that the patient is unable walk or sit up without assistance
* failure to feed
* multiple convulsions - more than two episodes in 24 h
* deep breathing, respiratory distress (acidotic breathing)
* circulatory collapse or shock, systolic blood pressure \< 70 mm Hg in adults and \< 50 mm Hg in children
* clinical jaundice plus evidence of other vital organ dysfunction

Complementary Laboratory findings (hospitals only)

* severe anaemia (Hb \< 5g/dl, packed cell volume \< 15%)
* hypoglycemia (blood glucose \< 2.2 mmol/l or \< 40 mg/dl)
* metabolic acidosis (plasma bicarbonate \< 15 mmol/l)
* serum creatinine \> 265 ìmol/l suggesting renal impairment

Exclusion Criteria:

Patients with known serious adverse reactions to quinine and artemisinin derivatives or patients who have received adequate antimalarial treatment 24 hours before admission will not be included in the study.

Women with known or suspected pregnancy in all trimesters will not be included in the study and will be treated with quinine infusions according to the new national DRC guidelines (Programme Nationale de Lutte contre le Paludisme, 2012). According to current routine procedures determination of pregnancy will be done by medical anamnesis and/ or by a positive pregnancy test.

Primary outcomes:
measure: Duration of hospitalization (from registration to discharge)
timeFrame: 3-7 days
Secondary outcomes:
Other outcomes:
measure: Clinical assessment
timeFrame: 28 days
measure: Laboratory assessment (exploratory - (see explanation in 1.1.4)
timeFrame: 28 days
measure: Time and motion study
timeFrame: 28 days
measure: Feasibility and acceptability study
timeFrame: 28 days
measure: Analysis of financial cost
timeFrame: 28 days
Locations:
city: Kimpese
country: Congo, The Democratic Republic of the
facility: Centre de Santé CECO
state: Bas Congo
city: Kimpese
country: Congo, The Democratic Republic of the
facility: Centre de Santé la Famille
state: Bas Congo
city: Kimpese
country: Congo, The Democratic Republic of the
facility: Hôpital Général de Référence IME
state: Bas Congo
city: Kisantu
country: Congo, The Democratic Republic of the
facility: Centre de Santé Ngeba
state: Bas Congo
city: Kisantu
country: Congo, The Democratic Republic of the
facility: Hôpital Saint Luc de Kisantu
state: Bas Congo
city: Maluku
country: Congo, The Democratic Republic of the
facility: Centre de Santé Bita
state: Kinshasa
city: Maluku
country: Congo, The Democratic Republic of the
facility: Centre de Santé Menkao
state: Kinshasa
city: Maluku
country: Congo, The Democratic Republic of the
facility: Centre Hospitalier d'État de Maluku
state: Kinshasa
city: Kinshasa
country: Congo, The Democratic Republic of the
facility: Centre Hospitalier Roi Baudoin 1er Masina
Study officials:
affiliation: Swiss Tropical & Public Health Institute
name: Christian Burri, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kinshasa School of Public Health
name: Antoinette Tshefu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dondorp AM, Fanello CI, Hendriksen IC, Gomes E, Seni A, Chhaganlal KD, Bojang K, Olaosebikan R, Anunobi N, Maitland K, Kivaya E, Agbenyega T, Nguah SB, Evans J, Gesase S, Kahabuka C, Mtove G, Nadjm B, Deen J, Mwanga-Amumpaire J, Nansumba M, Karema C, Umulisa N, Uwimana A, Mokuolu OA, Adedoyin OT, Johnson WB, Tshefu AK, Onyamboko MA, Sakulthaew T, Ngum WP, Silamut K, Stepniewska K, Woodrow CJ, Bethell D, Wills B, Oneko M, Peto TE, von Seidlein L, Day NP, White NJ; AQUAMAT group. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 2010 Nov 13;376(9753):1647-57. doi: 10.1016/S0140-6736(10)61924-1. Epub 2010 Nov 7.
citation: Dondorp A, Nosten F, Stepniewska K, Day N, White N; South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) group. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet. 2005 Aug 27-Sep 2;366(9487):717-25. doi: 10.1016/S0140-6736(05)67176-0.
citation: Lubell Y, Riewpaiboon A, Dondorp AM, von Seidlein L, Mokuolu OA, Nansumba M, Gesase S, Kent A, Mtove G, Olaosebikan R, Ngum WP, Fanello CI, Hendriksen I, Day NP, White NJ, Yeung S. Cost-effectiveness of parenteral artesunate for treating children with severe malaria in sub-Saharan Africa. Bull World Health Organ. 2011 Jul 1;89(7):504-12. doi: 10.2471/BLT.11.085878. Epub 2011 Apr 28.
citation: Centers for Disease Control and Prevention (CDC). Published reports of delayed hemolytic anemia after treatment with artesunate for severe malaria--worldwide, 2010-2012. MMWR Morb Mortal Wkly Rep. 2013 Jan 11;62(1):5-8.
citation: Ferrari G, Ntuku HM, Burri C, Tshefu AK, Duparc S, Hugo P, Mitembo DK, Ross A, Ngwala PL, Luwawu JN, Musafiri PN, Ngoie SE, Lengeler C. An operational comparative study of quinine and artesunate for the treatment of severe malaria in hospitals and health centres in the Democratic Republic of Congo: the MATIAS study. Malar J. 2015 May 30;14:226. doi: 10.1186/s12936-015-0732-1.