Status AsthmaticusNCT00750568
Intravenous Terbutaline in Severe Status Asthmaticus
An observational study of Status Asthmaticus, run by Wayne State University at 3 sites in United States.
Trial summary
Terbutaline is a medication that is used to treat serious asthma attacks (status asthmaticus). The purpose of this study is to determine if terbutaline is effective and safe when given as a continuous intravenous infusion to children ages 2 years to 18 years of age. Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Status Asthmaticus
- Type of treatment
- Injection or infusion
- How many people
- 36 participants
- Where
- 3 sitesUnited States
- Study dates
- Oct 2007to Aug 2009
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Inpatients in Pediatric ICU with a diagnosis of status asthmaticus
Who may be able to join
- Children 2 to 18 years of age.
- Admission to the ICU with a diagnosis of status asthmaticus.
- The pediatric intensivist taking care of the patient has decided to initiate intravenous terbutaline therapy.
- An indwelling venous catheter or arterial catheter that was placed for routine ICU monitoring.
- Informed consent obtained from the patient's parents or legal guardian.
Who cannot join
- Existing cardiovascular disease.
- History of bronchopulmonary dysplasia.
- Prior inclusion in this study.
- Known hypersensitivity to terbutaline, or prior adverse event associated with terbutaline.
- Terbutaline use within 48 hours of initiation of the study.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Rainbow Babies and Childrens' Hospital
Cleveland, Ohio, 44106
Children's Hospital of Michigan
Detroit, Michigan, 48201
Kosair Children's Hospital
Louisville, Kentucky, 40202
About this study
Official title: Pharmacokinetics and Pharmacodynamics of Terbutaline Given as a Continuous Intravenous Infusion in Severe Status Asthmaticus
Terbutaline is a medication that is used to treat serious asthma attacks (status asthmaticus). The purpose of this study is to determine if terbutaline is effective and safe when given as a continuous intravenous infusion to children ages 2 years to 18 years of age. Children participating in this study are inpatients in the Intensive Care Unit with a diagnosis of status asthmaticus and are receiving terbutaline as part of their routine care. Blood samples and physiological assessments will be used to determine how the body is using terbutaline and how well it is working.
Read the detailed description
- Background: Asthma remains a significant source of morbidity and mortality in children. In the United States, more than 11 million people reported having an asthma attack in the year 2000, and more than 5 percent of all children younger than age 18 reported having asthma attacks. The trend of increasing asthma-associated morbidity and mortality that occurred during 1980-1995 has not continued for all measures. During 1995-1998, the rate of emergency department visits for asthma increased, while the rate of hospitalization and death decreased for all age groups, except children younger than age 15. Asthma remains a significant problem despite scientific advances that generated greater understanding of the mechanisms of asthma and the development of therapeutic approaches that can reduce morbidity. Status asthmaticus is a common diagnosis for admission to pediatric intensive care units (PICUs). Widely accepted treatment for status asthmaticus includes inhaled beta-2 agonists, systemic corticosteroids, and inhaled anticholinergic agents. The intravenous and/or subcutaneous administration of beta-2 agonists has been advocated in the treatment of severe asthma and is prescribed in current practice. Additional treatment regimens may include magnesium, theophylline, and/or heliox with some patients still requiring mechanical ventilation, anesthetic agents or extracorporeal membrane oxygenation. Beta-adrenergic receptor agonists are critical in the treatment of asthma. Their use frequently results in effective bronchodilation. Commonly used beta-adrenergic agonists are epinephrine, albuterol and terbutaline, with albuterol and terbutaline having an increased selectivity for beta-2 receptors. These agents can be given by inhaled, IV, subcutaneous or oral routes. In the United States inhaled albuterol is the drug and route of choice in a majority of circumstances. Regarding efficacy when administering medications via the inhaled route, one must take into account many factors including inhalation technique, inspiratory flow rate, inspiratory volume and mode of delivery. Several characteristic pathophysiological changes that occur during a severe asthma attack (near complete airway obstruction, low tidal volumes, mucus plugging) may preclude the delivery of inhaled particles to the area of the lung that is most affected. In these instances, intravenous beta-agonists should be considered. Because of cardiac related side effects that are more pronounced in non-selective beta-agonist therapy, a beta-2 receptor agonist should be administered. In the United States, terbutaline is the only approved intravenous beta-2 receptor agonist. Terbutaline is a sympathomimetic amine synthesized in the mid-1960's that has been shown by in vitro and in vivo pharmacologic studies in animals to exert a preferential effect on beta 2-adrenergic receptors (beta2-AR), such as those located in bronchial smooth muscle. It has been available for clinical use since the 1970's and has been approved by the FDA for use in the treatment of asthma in children. Terbutaline binds to the beta-2 adrenergic receptor resulting in Gs-protein stimulation which in turn activates adenylyl cyclase increasing intracellular levels of 3'-5' cyclic adenosine monophosphate (cAMP). cAMP then activates protein kinase A (PKA) that phosphorylates several proteins that contribute to smooth muscle relaxation and resultant bronchodilation.
- Hypothesis and Primary Objectives: Intravenous terbutaline by continuous infusion is effective in decreasing the severity of an acute asthma attack and is safe to use in children 2 years to 18 years old. Terbutaline has different pharmacokinetics when given by continuous infusion versus single dose administration.
- Study Design: Phase 2 clinical pharmacokinetic/pharmacodynamic trial in pediatric patients aged 2-18 years old who are receiving intravenous terbutaline for a severe asthma attack. Three groups of 12 children will be examined based on age for a total N of 36. The first group will be 2-6 years, the second group will be 6-12 years old and the third will be adolescents 12-18 years old. Treatment efficacy will be gauged by comparing scores of the modified pulmonary index (MPIS) as well as utilization of the rescue medication protocol (see below). Pharmacokinetics and pharmacodynamics will be determined by serum samples collected in 1-2 ml aliquots prior to infusion and at 20 minutes, 2, 4, 6, 8, 10, and 12 hours post infusion, or until clinical improvement necessitates discontinuation of the infusion if less than 12 hours.
- Study Components:
- Modified Pulmonary Index Score (MPIS): Children will be assessed for clinical changes during therapy by utilizing the modified pulmonary index score (MPIS) which is a combination of 6 physiologic parameters, each graded 0-3, the sum of which reflects pulmonary status. The MPIS was assessed for reproducibility and validity and was shown to be highly reproducible across groups of health care providers (nurses, physicians, respiratory therapists) and was a valid indicator of asthma severity in children.
- Terbutaline levels as determined by HPLC at designated times stated previously.
- Conditions
- Status Asthmaticus
- Keywords
- Bronchial asthma, Asthma, bronchial, Status Asthmaticus, Terbutaline sulfate
- Medical subject headings
- Status Asthmaticus, Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | * In-patient in the Pediatric Intensive Care Unit * Diagnosis of Status asthmaticus * Receiving a continuous infusion of terbutaline as part of their standard of care * Ages 2 years to 6 years | |
| Group 2 | * In-patient in the Pediatric Intensive Care Unit * Diagnosis of Status asthmaticus * Receiving a continuous infusion of terbutaline as part of their standard of care * Ages greater than 6 years to 12 years | |
| Group 3 | * In-patient in the Pediatric Intensive Care Unit * Diagnosis of Status asthmaticus * Receiving a continuous infusion of terbutaline as part of their standard of care * Ages greater than 12 years to 18 years |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of continuous terbutaline infusion
Measured: Prior to infusion; 20 minutes, 2, 4, 6, 8, 10, 12 hours post infusion
Secondary outcomes (3)
Modified Pulmonary Index Score (MPIS)
Measured: Assess every 4 hours while IV terbutaline is infusing, continuing for 8 hours after the infusion is discontinued
Physiologic parameters
Measured: Prior to terbutaline, 20 minutes post, then hourly during infusion
Side effects
Measured: Duration of continuous infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2008 (estimated)
- Study startOct 2007
- Primary completionAug 2009 (estimated)
- Study completionAug 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Status AsthmaticusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wayne State University
- Sponsor type
- University, hospital or other
- Investigators
- Kevin Valentine, M.D., Principal investigator, Children's Hospital of MichiganMary Lieh-Lai, M.D., Study chair, Children's Hospital of Michigan; Wayne State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00750568
- Sponsor's protocol ID
- 10904
- Status last verified
- Aug 2008
- First submitted
- 9 Sep 2008
- Last updated
- 10 Sep 2008
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Pharmacodynamics of Terbutaline Given as a Continuous Intravenous Infusion in Severe Status Asthmaticus
- ClinicalTrials.gov ID
- NCT00750568
- Acronym / sponsor ID
- 10904
- Conditions
- Status Asthmaticus
- Keywords
- Bronchial asthma, Asthma, bronchial, Status Asthmaticus, Terbutaline sulfate
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Wayne State UniversityUniversity, hospital or other
- Study start
- Oct 2007
- Primary completion
- Aug 2009 (estimated)
- Study completion
- Aug 2009 (estimated)
- First posted
- 10 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Terbutaline is a medication that is used to treat serious asthma attacks (status asthmaticus). The purpose of this study is to determine if terbutaline is effective and safe when given as a continuous intravenous infusion to children ages 2 years to 18 years of age. Children participating in this study are inpatients in the Intensive Care Unit with a diagnosis of status asthmaticus and are receiving terbutaline as part of their routine care. Blood samples and physiological assessments will be used to determine how the body is using terbutaline and how well it is working.
Detailed description
- Background: Asthma remains a significant source of morbidity and mortality in children. In the United States, more than 11 million people reported having an asthma attack in the year 2000, and more than 5 percent of all children younger than age 18 reported having asthma attacks. The trend of increasing asthma-associated morbidity and mortality that occurred during 1980-1995 has not continued for all measures. During 1995-1998, the rate of emergency department visits for asthma increased, while the rate of hospitalization and death decreased for all age groups, except children younger than age 15. Asthma remains a significant problem despite scientific advances that generated greater understanding of the mechanisms of asthma and the development of therapeutic approaches that can reduce morbidity. Status asthmaticus is a common diagnosis for admission to pediatric intensive care units (PICUs). Widely accepted treatment for status asthmaticus includes inhaled beta-2 agonists, systemic corticosteroids, and inhaled anticholinergic agents. The intravenous and/or subcutaneous administration of beta-2 agonists has been advocated in the treatment of severe asthma and is prescribed in current practice. Additional treatment regimens may include magnesium, theophylline, and/or heliox with some patients still requiring mechanical ventilation, anesthetic agents or extracorporeal membrane oxygenation. Beta-adrenergic receptor agonists are critical in the treatment of asthma. Their use frequently results in effective bronchodilation. Commonly used beta-adrenergic agonists are epinephrine, albuterol and terbutaline, with albuterol and terbutaline having an increased selectivity for beta-2 receptors. These agents can be given by inhaled, IV, subcutaneous or oral routes. In the United States inhaled albuterol is the drug and route of choice in a majority of circumstances. Regarding efficacy when administering medications via the inhaled route, one must take into account many factors including inhalation technique, inspiratory flow rate, inspiratory volume and mode of delivery. Several characteristic pathophysiological changes that occur during a severe asthma attack (near complete airway obstruction, low tidal volumes, mucus plugging) may preclude the delivery of inhaled particles to the area of the lung that is most affected. In these instances, intravenous beta-agonists should be considered. Because of cardiac related side effects that are more pronounced in non-selective beta-agonist therapy, a beta-2 receptor agonist should be administered. In the United States, terbutaline is the only approved intravenous beta-2 receptor agonist. Terbutaline is a sympathomimetic amine synthesized in the mid-1960's that has been shown by in vitro and in vivo pharmacologic studies in animals to exert a preferential effect on beta 2-adrenergic receptors (beta2-AR), such as those located in bronchial smooth muscle. It has been available for clinical use since the 1970's and has been approved by the FDA for use in the treatment of asthma in children. Terbutaline binds to the beta-2 adrenergic receptor resulting in Gs-protein stimulation which in turn activates adenylyl cyclase increasing intracellular levels of 3'-5' cyclic adenosine monophosphate (cAMP). cAMP then activates protein kinase A (PKA) that phosphorylates several proteins that contribute to smooth muscle relaxation and resultant bronchodilation.
- Hypothesis and Primary Objectives: Intravenous terbutaline by continuous infusion is effective in decreasing the severity of an acute asthma attack and is safe to use in children 2 years to 18 years old. Terbutaline has different pharmacokinetics when given by continuous infusion versus single dose administration.
- Study Design: Phase 2 clinical pharmacokinetic/pharmacodynamic trial in pediatric patients aged 2-18 years old who are receiving intravenous terbutaline for a severe asthma attack. Three groups of 12 children will be examined based on age for a total N of 36. The first group will be 2-6 years, the second group will be 6-12 years old and the third will be adolescents 12-18 years old. Treatment efficacy will be gauged by comparing scores of the modified pulmonary index (MPIS) as well as utilization of the rescue medication protocol (see below). Pharmacokinetics and pharmacodynamics will be determined by serum samples collected in 1-2 ml aliquots prior to infusion and at 20 minutes, 2, 4, 6, 8, 10, and 12 hours post infusion, or until clinical improvement necessitates discontinuation of the infusion if less than 12 hours.
- Study Components:
- Modified Pulmonary Index Score (MPIS): Children will be assessed for clinical changes during therapy by utilizing the modified pulmonary index score (MPIS) which is a combination of 6 physiologic parameters, each graded 0-3, the sum of which reflects pulmonary status. The MPIS was assessed for reproducibility and validity and was shown to be highly reproducible across groups of health care providers (nurses, physicians, respiratory therapists) and was a valid indicator of asthma severity in children.
- Terbutaline levels as determined by HPLC at designated times stated previously.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | –* In-patient in the Pediatric Intensive Care Unit * Diagnosis of Status asthmaticus * Receiving a continuous infusion of terbutaline as part of their standard of care * Ages 2 years to 6 years |
| Group 2 | – | –* In-patient in the Pediatric Intensive Care Unit * Diagnosis of Status asthmaticus * Receiving a continuous infusion of terbutaline as part of their standard of care * Ages greater than 6 years to 12 years |
| Group 3 | – | –* In-patient in the Pediatric Intensive Care Unit * Diagnosis of Status asthmaticus * Receiving a continuous infusion of terbutaline as part of their standard of care * Ages greater than 12 years to 18 years |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Inpatients in Pediatric ICU with a diagnosis of status asthmaticus
Key inclusion criteria (5 listed)
- Children 2 to 18 years of age.
- Admission to the ICU with a diagnosis of status asthmaticus.
- The pediatric intensivist taking care of the patient has decided to initiate intravenous terbutaline therapy.
- An indwelling venous catheter or arterial catheter that was placed for routine ICU monitoring.
- Informed consent obtained from the patient's parents or legal guardian.
Key exclusion criteria (5 listed)
- Existing cardiovascular disease.
- History of bronchopulmonary dysplasia.
- Prior inclusion in this study.
- Known hypersensitivity to terbutaline, or prior adverse event associated with terbutaline.
- Terbutaline use within 48 hours of initiation of the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Pharmacokinetics of continuous terbutaline infusion
Time frame: Prior to infusion; 20 minutes, 2, 4, 6, 8, 10, 12 hours post infusion
3 secondary outcomes
Modified Pulmonary Index Score (MPIS)
Time frame: Assess every 4 hours while IV terbutaline is infusing, continuing for 8 hours after the infusion is discontinued
Physiologic parameters
Time frame: Prior to terbutaline, 20 minutes post, then hourly during infusion
Side effects
Time frame: Duration of continuous infusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2008.
Related trials for Status Asthmaticus
Not yet recruiting
Efficacy of High-Dose Continuous Intravenous Magnesium Sulfate Infusion vs Standard Intravenous Magnesium Sulfate Therapy in Status Asthmaticus in the ED
Asthma Exacerbation, Emergency Department
RecruitingPhase 2
Pediatric Asthma Trial of Corticosteroid Heterogeneity (PATCH): Trial of Dexamethasone Versus Methylprednisolone for Pediatric Critical Asthma
Asthma (Diagnosis)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin Valentine, M.D. principal investigator
Children's Hospital of Michigan
Mary Lieh-Lai, M.D. study chair
Children's Hospital of Michigan; Wayne State University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Status Asthmaticus, run by Wayne State University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Sep 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics of continuous terbutaline infusion (time frame: Prior to infusion; 20 minutes, 2, 4, 6, 8, 10, 12 hours post infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2008.