Malaria Treatment With Injectable ArteSunate (MATIAS)

This study has been completed.
Sponsor:
Collaborator:
Medicines for Malaria Venture
Information provided by (Responsible Party):
Swiss Tropical & Public Health Institute
ClinicalTrials.gov Identifier:
NCT01828333
First received: March 14, 2013
Last updated: September 12, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention
Severe Malaria
Other: No intervention

Study Type: Observational
Study Design: Time Perspective: Prospective
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

Resource links provided by NLM:


Further study details as provided by Swiss Tropical & Public Health Institute:

Primary Outcome Measures:
  • Duration of hospitalization (from registration to discharge) [ Time Frame: 3-7 days ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Clinical assessment [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    • 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

  • Laboratory assessment (exploratory - (see explanation in 1.1.4) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    - Hemoglobin nadir during follow up period of 28 days

  • Time and motion study [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    - Cumulative staff time required for all steps of patient management, including drug administration

  • Feasibility and acceptability study [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    • 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)

  • Analysis of financial cost [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    - Total financial cost of patient management including treatment


Enrollment: 350
Study Start Date: April 2013
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Intravenous artesunate - new routine in DRC

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.

Other: No intervention
No intervention

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

Ages Eligible for Study:   2 Months and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01828333

Locations
Congo, The Democratic Republic of the
Hôpital Général de Référence IME
Kimpese, Bas Congo, Congo, The Democratic Republic of the
Centre de Santé CECO
Kimpese, Bas Congo, Congo, The Democratic Republic of the
Centre de Santé la Famille
Kimpese, Bas Congo, Congo, The Democratic Republic of the
Hôpital Saint Luc de Kisantu
Kisantu, Bas Congo, Congo, The Democratic Republic of the
Centre de Santé Ngeba
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 Menkao
Maluku, Kinshasa, Congo, The Democratic Republic of the
Centre de Santé Bita
Maluku, Kinshasa, Congo, The Democratic Republic of the
Centre Hospitalier Roi Baudoin 1er Masina
Kinshasa, Congo, The Democratic Republic of the
Sponsors and Collaborators
Swiss Tropical & Public Health Institute
Medicines for Malaria Venture
Investigators
Principal Investigator: Christian Burri, PhD Swiss Tropical & Public Health Institute
Principal Investigator: Antoinette Tshefu, MD Kinshasa School of Public Health
  More Information

Publications:

Responsible Party: Swiss Tropical & Public Health Institute
ClinicalTrials.gov Identifier: NCT01828333     History of Changes
Other Study ID Numbers: Swiss TPH P 001-01-12
Study First Received: March 14, 2013
Last Updated: September 12, 2013
Health Authority: Congo, Democratic Republic of the: Ministry of Health

Keywords provided by Swiss Tropical & Public Health Institute:
Malaria
Severe
Artesunate
Quinine
Democratic Republic of Congo

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Quinine
Artesunate
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Muscle Relaxants, Central
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Amebicides

ClinicalTrials.gov processed this record on July 22, 2014