Cotrimoxazole Versus Amoxicillin in the Treatment of Community Acquired Pneumonia in Children Aged 2-59 Months
Condition: Childhood Pneumonia
MeSH terms: Pneumonia
Study type: Interventional
Phase: Phase 3

Summary: 
      The investigators hypothesized that Oral amoxicillin (25mg/kg/dose bid) given to children
      aged 2-59 months with pneumonia, would lead to better clinical outcome on day three in 89.9%
      of the children compared to 77.0% of children receiving oral cotrimoxazole (8 mg/kg/dose
      trimethoprim, 40 mg/kg/dose sulphamethoxazole). A double blind randomized controlled trial
      was conducted in the Assessment Center of Mulago Hospital. Children with non-severe pneumonia
      were randomized to receive either oral amoxicillin (25 mg/kg/dose) or cotrimoxazole
      (trimethoprim 8 mg/kg and sulphamethoxazole 40 mg/kg) and followed up on day 3 and 5 of
      treatment. The primary outcome measures were normalization of respiratory rate by day 3 of
      treatment. Secondary outcome measures were antimicrobial susceptibility to cotrimoxazole and
      amoxicillin.
    

Detailed description: 
      A triage Nurse identified and recorded children aged 2- 59 months who presented with a
      history of cough, difficult breathing, or fast breathing (tachypnea) in the Assessment Center
      of Mulago Hospital. Children aged 2-11 months with a respiratory rate>50 breaths per minute
      and those aged 12-59 months with a respiratory rate of > 40 breaths per minute were enrolled
      into the study following informed consent from parents/caretakers. Clinical history included
      the patient's detailed record of the illness, previous medical history and antibiotic use in
      the current illness. The IMCI approach was particularly employed during history taking and
      examination. The Principle Investigator and the research assistant interviewed the caretakers
      using a structured questionnaire. 5 mls of blood was drawn from the ante cubital fossa for a
      complete blood count and blood cultures.In addition thin and thick blood smears for malaria
      parasites were taken using finger prick blood samples. Rapid HIV antibody test was done to
      determine the HIV serostatus of the children. Children less than 18 months with a positive
      antibody test were referred to the Paediatric Infectious Disease Clinic (PIDC) Mulago
      Hospital for a DNA-PCR test to confirm their HIV infection status. Study participants were
      placed in a well aerated room and subjected to sputum induction. The principal investigator,
      with the help of the research assistant and a nurse performed the procedure.

      The study patients were nebulised with salbutamol at a dose of 0.1mg/kg in 3ml of Normal
      saline. 3mls of 3% sterile saline was administered through a facemask nebuliser for about
      10-15 minutes.Sputum was obtained by expectoration (in children who could do it) or by
      nasopharyngeal suction in those who were unable to expectorate. Gram stain, ZN stain and
      culture and sensitivity was performed on sputum. Oxygen saturation was measured before and
      after sputum induction. For those children who had oxygen saturation of less than 92% or
      could not tolerate the sputum induction, the procedure was deferred to the following day when
      the children were more stable. However, they continued with treatment. Treatment assignment
      was concealed from patients, parents, and study personnel. Children assigned co-trimoxazole
      received active medicine (8 mg/kg/dose trimethoprim + 40 mg/kg/dose sulphamethoxazole) and
      amoxicillin placebo twice a day. Children assigned amoxicillin received active medicine (25
      mg/kg/dose) and co-trimoxazole placebo twice a day.A randomization scheme was developed using
      a table of random numbers generated by computer. Study participants were randomly assigned to
      treatment in blocks of 4 to 12. Both drugs and placebo were manufactured and packaged in
      volumes of 100mls and had the same color. Treatment was started as soon as patients were
      enrolled in the study after withdrawal of blood and sputum samples. Drug doses were
      calculated according to the body weight. Cotrimoxazole was given orally (syrup) in a dose of
      8mg/kg/dose trimethoprim, 40mg/kg/dose sulphamethoxazole and oral (syrup) amoxicillin in a
      dose of 25mg/kg/dose every 12 hours until a total of 5 days was reached. The study had two
      treatment arms; one arm was randomly assigned to receive active amoxicillin plus placebo
      cotrimoxazole orally and the other arm was randomly assigned to receive active cotrimoxazole
      with placebo amoxicillin two doses per day. The study nurse and the principle investigator
      demonstrated to the parent/caretaker how to give the study drugs by giving the first dose
      from the clinic. An explanation was given on how to give medication at home and the level of
      understanding was checked before leaving clinic. Caretakers were instructed not to give any
      other medications especially antibiotics other than those given in the hospital and were
      instructed to return to the clinic on day 3 and 5 of treatment. Paracetamol syrup was
      administered to febrile children at a dose of 15 mg/kg 4 - 6 hourly if their axillary
      temperature were 38.5 degrees Celsius and above. Vitamin A was given according to the
      national recommendation guidelines. Patients who were diagnosed with malaria from blood
      slides were given Arthemeter-Lumefantrine tablets. Other medications were as well given
      according to the presentation and the diagnosis.The day of enrollment was counted as day 0.
      After three days of treatment, patients were checked for general danger signs and assessed
      for cough or difficult breathing and the respiratory rate counted. Improvement was defined as
      slower respiratory rate (either back to normal range for age, or more than 5 breaths per
      minute lower compared to the previous evaluation), less fever, normal oxygen saturation and
      better appetite, then patients were requested to complete the 5 days antibiotics and final
      follow up on the day 5 of treatment.
    

Intervention name(s): Amoxicillin; Cotrimoxazole; Amoxicillin placebo; Cotrimoxazole placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Oral amoxicillin (25mg/kg/dose)for 5 days; Cotrimoxazole (8 mg/kg/dose trimethoprim + 40 mg/kg/dose sulphamethoxazole)
Other intervention name(s): AMOX; CTX
Intervention MeSH terms: Amoxicillin; Trimethoprim, Sulfamethoxazole Drug Combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Efficacy; children; pneumonia; cotrimoxazole; amoxicillin