Malaria Treatment With Injectable ArteSunate

Severe Malaria Clinical Trial

— MATIAS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01828333
• Other study ID #: Swiss TPH P 001-01-12
• Status: Completed
• Phase: N/A
• First received: March 14, 2013
• Last updated: September 12, 2013
• Start date: April 2013
• Est. completion date: June 2013

Study information

• Verified date: September 2013
• Source: Swiss Tropical & Public Health Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Congo, Democratic Republic of the: Ministry of Health
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 350
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Months and older

Eligibility

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

Time Perspective: Prospective

Related Conditions & MeSH terms

• Malaria
• Severe Malaria

Intervention

Other:
• No intervention
No intervention

Locations

Country	Name	City	State
Congo, The Democratic Republic o	Centre de Santé CECO	Kimpese	Bas Congo
Congo, The Democratic Republic o	Centre de Santé la Famille	Kimpese	Bas Congo
Congo, The Democratic Republic o	Hôpital Général de Référence IME	Kimpese	Bas Congo
Congo, The Democratic Republic o	Centre Hospitalier Roi Baudoin 1er Masina	Kinshasa
Congo, The Democratic Republic o	Centre de Santé Ngeba	Kisantu	Bas Congo
Congo, The Democratic Republic o	Hôpital Saint Luc de Kisantu	Kisantu	Bas Congo
Congo, The Democratic Republic o	Centre de Santé Bita	Maluku	Kinshasa
Congo, The Democratic Republic o	Centre de Santé Menkao	Maluku	Kinshasa
Congo, The Democratic Republic o	Centre Hospitalier d'État de Maluku	Maluku	Kinshasa

Sponsors (2)

Lead Sponsor	Collaborator
Swiss Tropical & Public Health Institute	Medicines for Malaria Venture

Country where clinical trial is conducted

Congo, The Democratic Republic of the, 

References & Publications (4)

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. — View 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. — View 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. Erratum in: Lancet. 2011 Jan 8;377(9760):126. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Clinical assessment	Time from start of IV/IM treatment to initiation of oral treatment; Parasite clearance time; Clinical status at discharge; Signs for tiredness and breathlessness at follow up	28 days	No
Other	Laboratory assessment (exploratory - (see explanation in 1.1.4)	- Hemoglobin nadir during follow up period of 28 days	28 days	No
Other	Time and motion study	- Cumulative staff time required for all steps of patient management, including drug administration	28 days	No
Other	Feasibility and acceptability study	Perceived feasibility of patient management (as assessed and graded by provider questionnaire); Perceived ease of application of drug treatment (as assessed and graded by provider questionnaire); Perceived quality of case management (including perceived adverse effects) by patient / caretaker (as assessed through patient / caretaker questionnaire)	28 days	No
Other	Analysis of financial cost	- Total financial cost of patient management including treatment	28 days	No
Primary	Duration of hospitalization (from registration to discharge)		3-7 days	No