Malaria Treatment With Injectable ArteSunate

Completed

• Conditions: Severe Malaria
• Interventions: Other: No intervention

• Registration Number: NCT01828333
• Lead Sponsor: Swiss Tropical & Public Health Institute

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.

Study Timeline

• Study First Submitted: 2013-03-14
• Study Start: 2013-04
• Study First Submitted QC: 2013-04-05
• Study First Posted: 2013-04-10
• Primary Completion: 2013-06
• Study Completion: 2013-06
• Status Verified: 2013-09
• Last Update Submitted: 2013-09-12
• Last Update Posted: 2013-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 350

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Intravenous artesunate - new routine in DRC	No intervention	350 patients to be enrolled A first study group with the currently used standard for treatment of severe malaria in the DRC, i.v. quinine, was enrolled from 21 October 2012 to 15 January 2013. This study was initially planned as limited scope implementation study with pure observational character (routine diagnosis and treatment, time and motion study, feasibility assessment and costing) and thus not registered. Due to additional publications on i.v. artesunate, non-routine testing for hemoglobin levels before and after treatment plus non-routine follow up was added: Registration of study at this point.

Primary Outcome Measures

Name	Time	Method
Duration of hospitalization (from registration to discharge)	3-7 days

Trial Locations

Locations (9)

Centre de Santé la Famille; 🇨🇩 Kimpese, Bas Congo, Congo, The Democratic Republic of the

Centre de Santé Bita; 🇨🇩 Maluku, Kinshasa, Congo, The Democratic Republic of the

Centre de Santé Menkao; 🇨🇩 Maluku, Kinshasa, Congo, The Democratic Republic of the

Centre Hospitalier Roi Baudoin 1er Masina; 🇨🇩 Kinshasa, Congo, The Democratic Republic of the

Hôpital Saint Luc de Kisantu; 🇨🇩 Kisantu, Bas Congo, Congo, The Democratic Republic of the

Centre Hospitalier d'État de Maluku; 🇨🇩 Maluku, Kinshasa, Congo, The Democratic Republic of the

Centre de Santé CECO; 🇨🇩 Kimpese, Bas Congo, Congo, The Democratic Republic of the

Hôpital Général de Référence IME; 🇨🇩 Kimpese, Bas Congo, Congo, The Democratic Republic of the

Centre de Santé Ngeba; 🇨🇩 Kisantu, Bas Congo, Congo, The Democratic Republic of the