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Impact of Oral Application of Gastrografin on the Meconium Evacuation in Very Low Birth Weight Infants

Sponsor
Nadja Haiden,MD (Other)
Overall Status
Completed
CT.gov ID
NCT01515696
Collaborator
(none)
96
Enrollment
2
Arms
40
Duration (Months)

Study Details

Study Description

Brief Summary

Gastrografin is a radiopaque contrast agent for the gastrointestinal tract (GIT) which can be applied orally or rectally. In neonatal intensive care, Gastrografin is used to detect otherwise radiologically invisible perforations or an insufficient GIT anastomosis after surgery. Furthermore it is used for the treatment of meconium ileus. Gastrografin has a strong osmotic effect and leads to water influx into the intestine lumen. Thereby the peristaltic movement is accelerated and the premature infant excretes stool during the hours following application. Therefore Gastrografin might be effective to mobilize meconium from small bowel and deep parts of the colon. The investigators hypothesized that enteral application of Gastrografin accelerates meconium evacuation in premature infants, and thereby enhances feeding tolerance in this population.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

In premature infants the establishment of proper gastrointestinal function is challenging and often associated with delayed meconium passage. Meconium evacuation depends on gestational age and birthweight: the more immature an infant is, the later meconium passage starts and the longer meconium passage lasts. The mean duration of meconium evacuation in premature infants with a gestational age below 30 weeks is 8 days, while mature infants excrete their meconium in 2 days. The obstruction of deep intestinal segments by tenacious, sticky meconium frequently leads to gastric residuals, a distended abdomen and delayed food passage. The time lag to full enteral feedings is extended, the probability to acquire infections due to intravenous access for parenteral nutrition increases and the hospital stay of the infant is prolonged. However, the relation between meconium passage and feeding tolerance remains controversial. While one study showed that there is little concordance between first meconium passage and feeding tolerance, an other one showed that rapid and complete excretion of meconium is crucial for oral feeding tolerance and has a positive effect on it. Recently, the investigators performed a prospective randomized trial to determine, whether repeated prophylactic applications of small volume glycerin enemas accelerate passage of meconium in very low birth weight (VLBW) infants. Disappointingly, application of enemas did not accelerate meconium evacuation. A possible reason for the ineffectiveness of glycerin enemas is that the volume used was too small to mobilize tenacious meconium sufficiently from the colon and small bowel.

Gastrografin is a radiopaque contrast agent for the gastrointestinal tract (GIT) which can be applied orally or rectally. In neonatal intensive care, Gastrografin is used to detect otherwise radiologically invisible perforations or an insufficient GIT anastomosis after surgery. Furthermore it is used for the treatment of meconium ileus. Gastrografin has a strong osmotic effect and leads to water influx into the intestine lumen. Thereby the peristaltic movement is accelerated and the premature infant excretes stool during the hours following application. Therefore Gastrografin might be more effective to mobilize meconium from small bowel and deep parts of the colon. The investigators hypothesized, that enteral application of Gastrografin accelerates meconium evacuation in premature infants, and thereby enhances feeding tolerance in this population. The objective of the present study is to determine whether the enteral application of the osmotic contrast agent Gastrografin® accelerates complete meconium excretion and improves feeding tolerance in very low birth weight infants.

Study Design

Study Type:
Interventional
Actual Enrollment :
96 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
Impact of Oral Application of Gastrografin on the Meconium Evacuation in Very Low Birth Weight Infants- a Phase 4 Study
Study Start Date :
Oct 1, 2007
Actual Primary Completion Date :
Oct 1, 2010
Actual Study Completion Date :
Feb 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Gastrografin

infants receive 3ml/kg Gastrografin + 6ml/kg sterile water

Drug: Gastrografin
Patients will receive 3ml Gastrografin + 6ml sterile water/kg as a single dose via a nasogastric tube during the first 24 hours of life.
Other Names:
  • Diatrizoate Meglumine, Diatrizoate Sodium
  • NDA-011245

    		•
    Placebo Comparator: Sterile water

    infants receive 9ml/kg sterile water

    Drug: Sterile water
    Patients will receive 9ml/kg sterile water as a single dose via a nasogastric tube during the first 24 hours of life.
    Other Names:
  • Sterile water (ANDA) #077393

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Time to Complete Meconium Evacuation in Days [days of life until until the complete meconium evacuation from birth up to 40 days of life]

      Time to complete meconium evacuation in days of life until the complete meconium evacuation from birth up to 40 days of life

    Secondary Outcome Measures

    1. Feeding Tolerance- Full Enteral Feedings [days of life from birth until an infant tolerates en enteral feeding volume of 140 ml/kg]

      full enteral feeding is defined in days of life from birth until an an infant tolerates an enteral feeding volume of 140ml/kg

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 24 Hours
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • premature infants with a birthweight < 1500g and a gestational age < 32 weeks
    Exclusion Criteria:

    • major congenital disorders

    • chromosomal aberrations

    • systemic metabolic disease and

    • pre-existing gastrointestinal abnormalities (i.e. Morbus Hirschsprung)

    • pre-existing conditions of severe hypotension

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Nadja Haiden,MD

    Investigators

    • Principal Investigator: Nadja Haiden, MD, Medical university of Vienna, Department of Pediatrics

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Nadja Haiden,MD, Assoc.Prof.MD., Medical University of Vienna
    ClinicalTrials.gov Identifier:
    NCT01515696
    Other Study ID Numbers:
    • 27112001
    • 2007-000851-33
    First Posted:
    Jan 24, 2012
    Last Update Posted:
    Jul 18, 2014
    Last Verified:
    Jun 1, 2014
    Keywords provided by Nadja Haiden,MD, Assoc.Prof.MD., Medical University of Vienna
    VLBW infant
    Meconium
    Enteral nutrition
    Meconium passage
    Additional relevant MeSH terms:
    Meconium Ileus
    Body Weight
    Birth Weight

    Study Results

    Participant Flow

    Recruitment Details 3 year study period 789 infants were eligible for enrollment in the study
    Pre-assignment Detail Six hundred ninety-three infants were excluded for the following reasons: informed consent was not obtained in time(n = 660), parental refusal (n = 21), and 12 infants died before randomization.
    Arm/Group Title Gastrografin Sterile Water
    Arm/Group Description infants received 3ml/kg Gastrografin + 6ml/kg sterile water once during the first 24 hours of life via gastric tube infants received 9ml/kg sterile water once during the first 24 hours of life via gastric tube
    Period Title: Overall Study
    STARTED 47 49
    COMPLETED 39 39
    NOT COMPLETED 8 10

    Baseline Characteristics

    Arm/Group Title Gastrografin Sterile Water Total
    Arm/Group Description infants receive 3ml/kg Gastrografin + 6ml/kg sterile water infants receive 9ml/kg sterile water Total of all reporting groups
    Overall Participants 47 49 96
    Age (Count of Participants)
    <=18 years
    47
    100%
    49
    100%
    96
    100%
    Between 18 and 65 years
    0
    0%
    0
    0%
    0
    0%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    27
    57.4%
    20
    40.8%
    47
    49%
    Male
    20
    42.6%
    29
    59.2%
    49
    51%
    Region of Enrollment (participants) [Number]
    Austria
    47
    100%
    49
    100%
    96
    100%
    birthweight (grams) [Median (Full Range) ]
    Median (Full Range) [grams]
    870
    (0)
    900
    (0)
    879
    (0)

    Outcome Measures

    1. Primary Outcome
    Title Time to Complete Meconium Evacuation in Days
    Description Time to complete meconium evacuation in days of life until the complete meconium evacuation from birth up to 40 days of life
    Time Frame days of life until until the complete meconium evacuation from birth up to 40 days of life

    Outcome Measure Data

    Analysis Population Description
    per protocol
    Arm/Group Title Gastrografin Sterile Water
    Arm/Group Description infants receive 3ml/kg Gastrografin + 6ml/kg sterile water infants receive 9ml/kg sterile water
    Measure Participants 39 39
    Median (Full Range) [days of life]
    7
    8
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Gastrografin, Sterile Water
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.61
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Method of Estimation Estimation Parameter Median Difference (Net)
    Estimated Value 1
    Confidence Interval () 95%
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Feeding Tolerance- Full Enteral Feedings
    Description full enteral feeding is defined in days of life from birth until an an infant tolerates an enteral feeding volume of 140ml/kg
    Time Frame days of life from birth until an infant tolerates en enteral feeding volume of 140 ml/kg

    Outcome Measure Data

    Analysis Population Description
    per protocol
    Arm/Group Title Gastrografin Sterile Water
    Arm/Group Description infants receive 3ml/kg Gastrografin + 6ml/kg sterile water infants receive 9ml/kg sterile water
    Measure Participants 39 39
    Median (Full Range) [days]
    19
    26.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Gastrografin, Sterile Water
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.05
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Method of Estimation Estimation Parameter Median Difference (Final Values)
    Estimated Value 7.5
    Confidence Interval () 95%
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Post-Hoc Outcome
    Title Necrotizing Enterocolitis
    Description necrotizing enterocolitis stage 2a after Bell
    Time Frame End of study

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Gastrografin Sterile Water
    Arm/Group Description infants receive 3ml/kg Gastrografin + 6ml/kg sterile water infants receive 9ml/kg sterile water
    Measure Participants 39 39
    Number [participants]
    8
    17%
    3
    6.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Gastrografin, Sterile Water
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value >0.05
    Comments
    Method Chi-squared
    Comments

    Adverse Events

    Time Frame from birth until discharge of the infant with a maximum of 5 months
    Adverse Event Reporting Description
    Arm/Group Title Gastrografin Sterile Water
    Arm/Group Description infants receive 3ml/kg Gastrografin + 6ml/kg sterile water infants receive 9ml/kg sterile water
    All Cause Mortality
    Gastrografin Sterile Water
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Gastrografin Sterile Water
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 43/47 (91.5%) 42/49 (85.7%)
    Cardiac disorders
    persistent ductus arteriosus 22/47 (46.8%) 22 28/49 (57.1%) 28
    Congenital, familial and genetic disorders
    death 8/47 (17%) 8 7/49 (14.3%) 7
    Gastrointestinal disorders
    necrotizing enterocolitis 10/47 (21.3%) 10 4/49 (8.2%) 4
    Nervous system disorders
    intraventricular haemorrhage 3/47 (6.4%) 3 3/49 (6.1%) 3
    Other (Not Including Serious) Adverse Events
    Gastrografin Sterile Water
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/47 (10.6%) 6/49 (12.2%)
    Infections and infestations
    culture proven sepsis 5/47 (10.6%) 5 6/49 (12.2%) 6

    Limitations/Caveats

    [Not Specified]

    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 Nadja Haiden M.D.
    Organization Medical University of Vienna
    Phone +431404003232
    Email nadja.haiden@meduniwien.ac.at
    Responsible Party:
    Nadja Haiden,MD, Assoc.Prof.MD., Medical University of Vienna
    ClinicalTrials.gov Identifier:
    NCT01515696
    Other Study ID Numbers:
    • 27112001
    • 2007-000851-33
    First Posted:
    Jan 24, 2012
    Last Update Posted:
    Jul 18, 2014
    Last Verified:
    Jun 1, 2014