Caffeine Citrate for the Treatment of Apnea Associated With Bronchiolitis in Young Infants
Condition: Bronchiolitis; Apnea; Caffeine
MeSH terms: Bronchiolitis; Apnea
Study type: Interventional

Summary: 
      Viral bronchiolitis is the most common lower respiratory tract infection of infancy. Apnea is
      a complication of bronchiolitis, reported in 16 - 21% of cases. Caffeine, a
      trimethylxanthine, acts as an antagonist to endogenous adenosine and a potent central nervous
      system stimulant. In apnea of prematurity, caffeine is believed to work by increasing central
      respiratory drive.

      Infants ≤4 months of age, presenting to pediatric emergency center Al-Sadd, from September
      2011 to May 2014, with a diagnosis of viral bronchiolitis associated with apnea.

      A randomized, double-blind, controlled trial with a sample size of 45 patients per group

      Data Collection methods, instruments used measurements:

      Randomization:

      In the emergency department, the patients will be assigned to either one of the two
      treatments using a computer-generated randomized numbers in a 1:1 ratio. Pharmacy will
      prepare sequential sealed vials containing the experimental drugs. Randomization code will be
      revealed only after all patients completed the study. The medical team in addition to the
      patients will be blinded to the medication delivered. There will be no detectable difference
      in the color, smell of the two study treatments.

      Guardians or parents of eligible infants will be approached regarding the study, explaining
      the purpose and the treatment modalities. Patients will be included after obtaining a verbal
      and written consent.

      Study Intervention:

      Treatment 1: Single stat dose (25 mg per kilogram of body weight) of intravenous caffeine
      citrate (25mg caffeine citrate equal to 12.5mg caffeine base).

      Treatment 2: Placebo with an equivalent volume of normal saline. Calculated study medications
      will be diluted with Dextrose 5% in Water to 20 ml and will be given intravenous over 30
      minutes using syringe infusion pump.

      After random assignment, eligible infants will receive one of the study treatments.
      Non-pharmacological therapies may be used as necessary to control apnea. Antibiotics and
      antipyretics may be used as per the discretion of the treating physician.

      After stabilization of patients as usually done in Pediatric Emergency Center , patients will
      be admitted to pediatric intensive care unit (PICU) for further monitoring monitoring when
      indicated.
    

Detailed description: 
      Study area/setting:

      Pediatric emergency center Al-Sadd, (PEC) is the main pediatric emergency centre in the state
      of Qatar with approximately 200,000 visits annually. It has a capacity of 42 observation beds
      providing most of the inpatient facilities except for intensive care monitoring. Patients
      admitted to the Pediatric Emergency Center are managed there until discharged home unless an
      Intensive Care Unit admission is required.

      Study Subjects:

        -  Inclusion criteria: Infants ≤4 months of age, presenting to pediatric emergency center
           Al-Sadd, from September 2011 to May 2014, with a diagnosis of viral bronchiolitis
           associated with apnea.

        -  Exclusion criteria:

             -  Hypersensitivity to caffeine.

             -  Patients on caffeine treatment.

             -  Cardiovascular congenital abnormalities.

             -  Infants with a previous diagnosis of gastroesophageal reflux disease.

             -  Hypoglycemia and/or electrolytes disorders.

             -  Suspected sepsis.

             -  Seizure disorders.

             -  Inborn errors of metabolism.

             -  Renal and/or hepatic impairment.

             -  Major congenital anomalies of the upper and lower respiratory tract (severe
                tracheomalacia, trachea-esophageal fistula, diaphragmatic hernia, congenital lobar
                emphysema, congenital cystic adenomatoid malformation).

      Study Design: A randomized, double-blind, controlled trial.

      Sample Size:

      In a retrospective chart review for all patients admitted to our institutions PICU/step-down
      unit with bronchiolitis associated with apnea in 2010, 87 patients were identified, 52
      patients (60%) were apnea free after 12 hours from admission. To enable detection of a 50%
      improvement for the investigated group in resolution of apnea after 12 hours with 90% power
      and two sided alpha= 0.05, we estimated 42 patients per group is required. To compensate for
      dropouts, we planned to recruit 90 patients altogether.

      Data Collection methods, instruments used measurements:

      Randomization:

      In the emergency department, the patients will be assigned to either one of the two
      treatments using a computer-generated randomized numbers in a 1:1 ratio. Pharmacy will
      prepare sequential sealed vials containing the experimental drugs. Randomization code will be
      revealed only after all patients completed the study. The medical team in addition to the
      patients will be blinded to the medication delivered. There will be no detectable difference
      in the color, smell of the two study treatments.

      Guardians or parents of eligible infants will be approached regarding the study, explaining
      the purpose and the treatment modalities. Patients will be included after obtaining a verbal
      and written consent.

      Study Intervention:

      Treatment 1: Single stat dose (25 mg per kilogram of body weight) of intravenous caffeine
      citrate (25mg caffeine citrate equal to 12.5mg caffeine base).

      Treatment 2: Placebo with an equivalent volume of normal saline.

      Calculated study medications will be diluted with D5W to 20 ml and will be given intravenous
      over 30 minutes using syringe infusion pump.

      After random assignment, eligible infants will receive one of the study treatments.
      Non-pharmacologic therapies such as supplemental oxygen, non invasive respiratory support,
      endotracheal intubation and mechanical ventilation may be used as necessary to control apnea.
      Antibiotics and antipyretics may be used as per the discretion of the treating physician.

      After stabilization of patients as usually done in pediatric emergency center , patients will
      be admitted to Pediatric Intensive Care Unit for further monitoring when indicated.
    

Intervention name(s): Caffeine citrate; Normal saline
Intervention type(s): Drug; Drug
Intervention description(s): Single stat dose (25 mg per kilogram of body weight) of intravenous caffeine citrate (25mg caffeine citrate equal to 12.5mg caffeine base).; Placebo with an equivalent volume of normal saline.
Other intervention name(s): arm 1; arm2
Intervention MeSH terms: Caffeine; Caffeine citrate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: caffeine; apnea; bronchiolitis