Medical Treatment for Gastroesophageal Reflux Disease (GERD) in Preterm Infants
Study Details
Study Description
Brief Summary
Study Question: In premature infants with apnea and/or bradycardia attributed to gastroesophageal reflux disease (GERD), does treatment with medications (acid blockers and motility agents), compared to placebo, reduce the frequency of apnea and bradycardia?
Background: Many clinicians believe that apnea and bradycardia in preterm infants may be caused by gastroesophageal reflux (GER), however, studies have failed to demonstrate even a temporal association between episodes of GER and apnea. There have been no prospective randomized trials of treatment for GERD in preterm infants with apnea or other symptoms attributed to GER.
Methods: A randomized, cross-over study will be performed. This cross-over design will provide the patient's clinician with unbiased information about the patient's response to treatment. The clinician can use this information in deciding whether or not to continue treatment after the two-week study period.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Study Question: In premature infants with apnea and/or bradycardia attributed to GERD, does treatment with H2 blockers and prokinetic agents, compared to placebo, reduce the frequency of apnea and bradycardia?
Background: The incidence of gastroesophageal reflux (GER) has been reported in as many as 50% of healthy term infants and 63% of preterm infants. Anecdotal observations of apnea and bradycardia clustered around feedings or with an episode of vomiting have suggested to clinicians that apnea and bradycardia in preterm infants may be caused by reflux, however, studies have failed to demonstrate even a temporal association between episodes of GER and apnea. One retrospective study concluded that anti-reflux medications did not reduce the frequency of apnea in premature infants. There have been no prospective randomized trials of treatment for GERD in preterm infants with apnea or other symptoms attributed to GER. Despite the lack of evidence supporting a causal relationship between GER and respiratory problems in preterm infants and the lack of data regarding the efficacy or safety of the treatments for GERD, many clinicians continue to believe that GER causes respiratory symptoms in preterm infants and these infants are commonly treated with medications for GERD.
Specific aims: To determine whether medications for GER are effective in reducing respiratory symptoms attributed to GER.
Methods: A randomized, controlled masked cross-over study will be performed. The cross-over design will prevent evaluation of long-term outcomes but will increase the power to evaluate short-term outcomes by using the patient as his/her own control. This cross-over design will also provide the patient's clinician with unbiased information about the patient's response to treatment. The clinician can use this information in deciding whether or not to continue treatment after the two-week study period. This approach for making therapeutic decisions in individual patients has been described as an "N of 1" trial.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Anti-reflux Medications, then Placebo (group 1) 3-day course of anti-reflux medications, followed by 7-day course placebo, followed by 4-day course anti-reflux medications. All study medication administered via nipple or orogastric (OG) tube. Metaclopramide (anti-reflux) given in 0.1mg/kg/dose q6hrs, 30min. prior to feedings. Ranitidine, 3mg/kg/dose, q12hrs. Saline placebo at same respective volumes. |
Drug: Metaclopramide
Drug: Ranitidine
Drug: placebo
|
| Other: Placebo, then Anti-reflux Medications 3-day course placebo, followed by 7-day course anti-reflux medication, followed by 4-day course placebo. All study medication administered via nipple or OG tube. Metaclopramide (anti-reflux) given in 0.1mg/kg/dose q6hrs, 30min. prior to feedings. Ranitidine, 3mg/kg/dose, q12hrs. Saline placebo at same respective volumes. |
Drug: Metaclopramide
Drug: Ranitidine
Drug: placebo
|
Outcome Measures
Primary Outcome Measures
- Bradycardia Episodes/Day [7 days]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Premature infants < 37 weeks gestation at birth; currently less than 44 weeks postmenstrual age.
-
Not currently receiving mechanical ventilation
-
Clinical diagnosis of GER and apnea/bradycardia suspected by the clinicians to be related to the GER. (Supporting diagnostic test information, such as upper gastrointestinal series [UGI] studies and pH probes will be recorded but not required for study enrollment.)
-
Attending physician plan to begin anti-reflux medications
-
Infants may be included in the study if they are on continuous positive airway pressure (CPAP) or methylxanthines for treatment of apnea only if the clinicians are willing to maintain the same regimen for the two-week duration of the study.
-
Stable feeding regimen
Exclusion Criteria:
-
History of congenital neurological defect
-
Imminent discharge (within 2 weeks)
-
Parent refusal
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memorial Hermann Children's Hospital | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- The University of Texas Health Science Center, Houston
Investigators
- Principal Investigator: Kathleen A Kennedy, MD, MPH, University of Texas
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GERD
Study Results
Participant Flow
| Recruitment Details | participants = premature infants, <36 weeks gestation at birth, recruited from NICU at a hospital in Houston, Texas,USA, between 2004-2009 |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Medications, Placebo, Medications (Group 1) | Placebo, Medications, Placebo (Group 2) |
|---|---|---|
| Arm/Group Description | 3-day course of anti-reflux medications, followed by 7-day course placebo, followed by 4-day course anti-reflux medications. All study medication administered via nipple or OG tube. Metaclopramide (anti-reflux) given in 0.1mg/kg/dose q6hrs, 30min. prior to feedings. Ranitidine, 3mg/kg/dose, q12hrs. Saline placebo at same respective volumes. | received 3-day course placebo, followed by 7-day course anti-reflux medication, followed by 4-day course placebo. All study medication administered via nipple or OG tube. Metaclopramide (anti-reflux) given in 0.1mg/kg/dose q6hrs, 30min. prior to feedings. Ranitidine, 3mg/kg/dose, q12hrs. Saline placebo at same respective volumes. |
| Period Title: Intervention 1 (3-day Course) | ||
| STARTED | 9 | 9 |
| COMPLETED | 8 | 9 |
| NOT COMPLETED | 1 | 0 |
| Period Title: Intervention 1 (3-day Course) | ||
| STARTED | 8 | 9 |
| COMPLETED | 8 | 9 |
| NOT COMPLETED | 0 | 0 |
| Period Title: Intervention 1 (3-day Course) | ||
| STARTED | 8 | 9 |
| COMPLETED | 8 | 9 |
| NOT COMPLETED | 0 | 0 |
| Period Title: Intervention 1 (3-day Course) | ||
| STARTED | 8 | 9 |
| COMPLETED | 8 | 9 |
| NOT COMPLETED | 0 | 0 |
| Period Title: Intervention 1 (3-day Course) | ||
| STARTED | 8 | 9 |
| COMPLETED | 8 | 9 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | All Study Participants |
|---|---|
| Arm/Group Description | |
| Overall Participants | 17 |
| Age (Count of Participants) | |
| <=18 years |
17
100%
|
| Between 18 and 65 years |
0
0%
|
| >=65 years |
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
0.1
(0.06)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
12
70.6%
|
| Male |
5
29.4%
|
| Region of Enrollment (participants) [Number] | |
| United States |
17
100%
|
Outcome Measures
| Title | Bradycardia Episodes/Day |
|---|---|
| Description | |
| Time Frame | 7 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| 18 participants originally enrolled, 1 withdrew, leaving 17 participants analyzed. |
| Arm/Group Title | Medications | Placebo |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 17 | 17 |
| Mean (Standard Deviation) [episodes per day] |
4.6
(3.1)
|
3.6
(2.7)
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety population include only those who received study intervention. | |||
| Arm/Group Title | Medications | Placebo | ||
| Arm/Group Description | ||||
All Cause Mortality |
||||
| Medications | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Medications | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/17 (0%) | 0/17 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Medications | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/17 (0%) | 0/17 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Kathleen A. Kennedy, MD, MPH |
|---|---|
| Organization | UT Houston Medical School |
| Phone | 713 500-6708 |
| kathleen.a.kennedy@uth.tmc.edu |
- GERD