Study to Compare Feasibility of 1-step Injectable Artesunate vs. Conventional 2-step Injectable Artesunate
Condition: Severe Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 2

Summary: 
      The objectives of this study contains 3 parts: (1) a comparison of 1-step parenteral
      artesunate (AS) versus conventional 2-step parenteral artesunate in patients with severe
      malaria to assess the feasibility of administration, parasite and fever clearance times in
      two countries, (2) a quantification of convenience and costs of the new 1-step artesunate
      parenteral formulation versus the conventional formulation in a randomised study, (3) A cost
      analysis of 1-step parenteral artesunate using data from Part 1 & Part 2. This will assess
      health facility-level costs, and also health system costs to encompass all costs of a
      potential change from conventional to 1-step artesunate, including re-training, materials,
      and drug replacement.

      The conventional formulation of injectable artesunate requires a 2-step reconstitution and
      dilution of the artesunate hemisuccinate powder. A new formulation of injectable artesunate
      has been developed by Fosun Pharma requiring a simpler 1-step reconstitution. Bioequivalence
      of the new formulation to the conventional formulation.

      For part 1, a total number of participants of this study would be 200 participants, estimated
      100 per site will be recruited. For part 2, a total number of 40 semi-structured interviews
      with study staff, health staff, policy makers, and stake holders; and survey/questionnaires
      with 150 health staff.
    

Detailed description: 
      Study design:

      Part 1

      A comparison of 1-step parenteral artesunate vs. conventional 2-step parenteral artesunate in
      patients with severe malaria to assess the feasibility of administration, parasite and fever
      clearance times of 1-step parenteral artesunate to conventional artesunate in 2 countries.
      Patients with severe malaria will be enrolled and randomly allocated to treatment with
      conventional injectable artesunate or 1-step injectable artesunate. A physical examination
      will be performed daily and every six hours on indication. Vital signs rec-orded hourly for
      unstable patients, then 6 hourly for stabilised patients, and at each follow-up visit. A
      symptom questionnaire will be taken daily to help identify adverse events. Patients will be
      asked to come back for a follow-up visit at day 7, 14, 21 and 28. Patients will not be
      followed up longer. In case of unresolved important sequelae at day 28, the patient will be
      followed and treated longer in order to provide the appropriate clinical care.

      A Time and Motion study will record the time to prepare the artesunate solution for injection
      and administer treatment, number of actions performed to prepare treatment, and consumables
      used. Clinical, parasitological, and laboratory assessments will be recorded while patients
      are admitted in hospital and then weekly up to day 28 to assess recovery and determine final
      status.

      Part 2

      A mixed method social science study that entails semi-structure interviews and survey with
      study staff (involved in part 1), health workers (who treat severe malaria) and policymakers
      and stakeholders (who are involved in devising national malaria policy and its
      implementation), to assess the acceptability, feasibility, pros and cons, costs, and
      logistics and training implications of 1-step artesunate vs conventional artesunate. For both
      sites, semi-structure interviews will be conducted with minimum of a total of 40 respondents
      consisting of study staff, health staff and policy makers and stakeholders. The ultimate
      sample for semi-structure interviews will be dependent on the data saturation. For
      survey/questionnaire, a maximum number of relevant participants (study staff and health care
      staff) will be attempted to be recruited from two sites. A minimum of 150 study staff and
      health care staff will be recruited in the survey.

      Part 3

      A cost analysis of 1-step parenteral artesunate using data from Part 1 & Part 2. This will
      assess health facility-level costs, and also health system costs to encompass all costs of a
      potential change from conventional to 1-step artesunate, including re-training, materials,
      drug replacement.

      In addition to time measurement, the observer will also record the resources used for the
      administration of artesunate. This will include the vials themselves, as well as other
      consumables required for the administration (syringes, needles, catheters, etc.).

      Funder: Shanghai Fosun Pharmaceutical Industrial Development Co., Ltd
    

Intervention name(s): Argesun 60mg (1 step parenteral artesunate); Artesun 60mg (2-step parenteral artesunate)
Intervention type(s): Drug; Drug
Intervention description(s): Each vial of powder contains 60mg artesunate. Each ampoule of 6 ml solvent contains: sodium bicarbonate 8.4mg/ml; arginine 20mg/ml.; Each vial of powder contains 60 mg artesunate. Each ampoule of 1 ml solvent contains 50 mg sodium bicarbonate. Each ampoule of 5 ml diluent contains 45 mg sodium chloride.
Intervention MeSH terms: Artesunate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Parenteral artesunate