Caffeine Citrate for the Treatment of Apnea Associated With Bronchiolitis in Young Infants

March 31, 2015 updated by: Hamad Medical Corporation

Caffeine Citrate for the Treatment of Apnea Associated With Bronchiolitis in Young Infants: A Randomized, Double Blind, Controlled Trial (RCT)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Qatar
      • Doha, Qatar, 3050
        • Pediatric Emergency Center, Hamad Medical Corporation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 day to 4 months (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: caffeine Citrate
Drug: Caffeine citrate
Single stat dose (25 mg per kilogram of body weight) of intravenous caffeine citrate (25mg caffeine citrate equal to 12.5mg caffeine base).
Other Names:
  • arm 1
Placebo Comparator: Normal saline
Drug: Normal saline
Placebo with an equivalent volume of normal saline.
Other Names:
  • arm2

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
The primary efficacy outcome in this double-blinded study was the time until last apnea episode in both groups.
Time Frame: 2 year 8 mongths
2 year 8 mongths

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The proportion of patients with apnea resolution at 12 hours in both groups,
Time Frame: 2 year and 8 months
2 year and 8 months
The frequency of apnea in the first 24, 48 and 72 hours after medication administration for both arms
Time Frame: 2 year and 8 months
2 year and 8 months
The duration of apnea in the first 24, 48, and 72 hours after medication administration for both arms
Time Frame: 2 year and 8 months
2 year and 8 months
Invasive and non-invasive respiratory support needed in both groups.
Time Frame: 2 year 8 months
2 year 8 months
The length of oxygen therapy needed in both groups.
Time Frame: 2 year 8 months
2 year 8 months
The time until feeding was tolerated in both groups.
Time Frame: 2 year 8 months
2 year 8 months
The length of PICU/step-down unit stay in both groups.
Time Frame: 2 year 8 months
2 year 8 months
The overall length of hospital stay in both groups.
Time Frame: 2 year 8 months
2 year 8 months
Spot heart rate in both groups was compared every 4 hours from enrollment for up to three days.
Time Frame: 2 year 8 months
As a safety measure, spot heart rate was compared every 4 hours from enrollment for up to three days.
2 year 8 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hamad Medical Corporation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: dr. Khalid Al-ansari, MD,FAAP, consultant pediatric emergency

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 8, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 15, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 16, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 1, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 31, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • #11146/11

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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