SSALT: Sodium Supplementation and Growth in Very Low Birth Weight Infants

• Sponsor: Children's Hospital Medical Center, Cincinnati (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01795638
• Collaborator: University of Cincinnati (Other)
• Enrollment: 53
• Location: 1
• Arms: 2
• Duration (Months): 15
• Patients Per Site Per Month: 3.5

Study Details

Study Description

Brief Summary

Adequate growth during the neonatal period is critical for optimal long term outcomes. Despite maximal calorie intake, sixty percent of very low birth weight infants still fail to thrive suggesting that factors other than total calorie intake are important in ensuring consistent weight gain. Several reports have indicated a positive sodium balance is critical in ensuring good weight gain in very low birth weight infants, however these infants are susceptible to low serum sodium concentrations. Urine sodium values are sometimes used to diagnosis of hyponatremia or negative sodium balance after the first two weeks of life, but there is no evidence for this practice in preterm neonates. Our central hypothesis is that early supplementation with sodium will ensure positive sodium balance in very low birth weight infants and will result in optimal weight gain and enhanced long term outcomes. Secondarily we hypothesize that low sodium concentrations in the urine will not correlate with low serum sodium values.

Condition or Disease	Intervention/Treatment	Phase
Extreme Immaturity	Drug: Sodium chloride; Drug: Placebo	Phase 4

Detailed Description

This is a randomized, blinded, placebo-controlled trial in infants born at less than 32 weeks gestation, who are admitted to the Newborn Intensive Care Unit at University of Cincinnati Medical Center, Cincinnati, Ohio. Infants are randomized to receive either 4 meq/kg/day supplemental sodium or an equal amount of sterile water on days of life 7-35. Institutional data from 2008 revealed that a sample size of 56 infants completing the study will detect a 15% difference in the primary outcome of weight gain with 80% power and an alpha error of 0.05. Allowing that 33% drop-out rate (infants may be transferred to another hospital, expire, or be discharged prior to day of life 35), we choose to randomize 75 infants. Calorie intake, serum sodium, weight gain, urine sodium were monitored weekly till 35 days of life or discharge. Infants were assessed for common morbidities associated with prematurity including bronchopulmonary dysplasia, systemic hypertension, late-onset sepsis, necrotizing enterocolitis and retinopathy of prematurity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Prevention
• Official Title: Impact of Early Postnatal Sodium Supplementation on Weight Gain in Very Low Birth Weight Infants
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Sodium chloride Sodium chloride 1 meq/kg (0.4 ml/kg of 2.5meq/ml formulation for injection)q6hrs on days of life 7-35. Intervention was given enterally if feedings were at least 100 ml/kg/day; otherwise medication was diluted in equal amounts of dextrose 5% water and administered intravenously.	Drug: Sodium chloride
Placebo Comparator: sterile water Sterile water, 0.4 ml/kg q6hrs on days of life 7-35. Placebo is given enterally when infant is tolerating at least 100 ml/kg/day; otherwise the product is diluted in equal amounts of dextrose 5% water and administered intravenously.	Drug: Placebo; sterile water, 0.4 ml/kg every 6 hours on days of life 7-35.; Other Names: Sterile Water

Outcome Measures

Primary Outcome Measures

1. Weight Gain at Six Weeks of Age [Six weeks of age]

   Average weight gain in g/kg/day and also as a % birthweight over the first six weeks of the study will be compared between the two study arms

Secondary Outcome Measures

1. Body Length at Six Weeks of Age [six weeks of age]

   The percentage of infants maintaining birth percentile at six weeks between the two study arms will be analyzed

2. Head Circumference [six weeks of age]

   The percentage of infants maintaining birth percentile for head circumference will be compared between the two groups.

3. Mean Systolic Blood Pressure [36 weeks post-conceptual age]

   Systolic blood pressures at 36 weeks post-conceptual age will be compared between the two groups

4. Chronic Diuretic Therapy [patients will be followed during birth hospital stay; an expected average of 3 months of age]

   The incidence of chronic diuretic therapy will be compared between the two groups

5. Late-onset Sepsis [patients will be followed during birth hospitalization; an expected average of 3 months of age]

   The incidence of late-onset sepsis, defined as positive blood culture for credible pathogen and/or 5 days of continuous antimicrobial therapy after the first week of life will be compared between the two groups.

6. Necrotizing Enterocolitis [patients will be followed during birth hospitalization; an expected average of 3 months of age]

   The incidence of Bell stage II or greater necrotizing enterocolitis after the second week of life will be compared between the two groups

7. Chronic Lung Disease [36 weeks post-mentrual age]

   The incidence of chronic lung disease, defined as respiratory support at 36 weeks postmenstrual age will be compared between the two groups

8. Mortality [patients will be followed during birth hospitalization; an expected 3 months of age]

   The incidence of death during birth hospitalization will be compared between the two study arms

9. Patent Ductus Arteriosus [After the second week of life]

   prolonged Patent Ductus Arteriosus after the second week of life

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Days to 8 Days
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• infants born at less than 32 weeks postmenstrual age

Exclusion Criteria:

• infants with major malformations deemed incompatible with life disease states characterized by edema renal failure, defined as an increase in serum creatinine by 0.5 mg/dl/day or urine output less than 0.5 ml/kg/hour

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45229

Sponsors and Collaborators

• Children's Hospital Medical Center, Cincinnati
• University of Cincinnati

Investigators

• Study Director: Henry T Akinbi, MD, Cincinnati Childrens Hospital Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Children's Hospital Medical Center, Cincinnati
• ClinicalTrials.gov Identifier: NCT01795638
• Other Study ID Numbers: 09-07-28-07
• First Posted: Feb 21, 2013
• Last Update Posted: Sep 7, 2020
• Last Verified: Mar 1, 2016

• Keywords provided by Children's Hospital Medical Center, Cincinnati: anthropometrics; weight; nutrition
• Additional relevant MeSH terms: Birth Weight

Study Results

Participant Flow

Arm/Group Title	Intervention	Placebo
Arm/Group Description	Sodium chloride 1 meq/kg (0.4 ml/kg of 2.5meq/ml formulation for injection)q6hrs on days of life 7-35. Intervention was given enterally if feedings were at least 100 ml/kg/day; otherwise medication was diluted in equal amounts of dextrose 5% water and administered intravenously. Sodium chloride	Sterile water, 0.4 ml/kg q6hrs on days of life 7-35. Placebo is given enterally when infant is tolerating at least 100 ml/kg/day; otherwise the product is diluted in equal amounts of dextrose 5% water and administered intravenously. Placebo: sterile water, 0.4 ml/kg every 6 hours on days of life 7-35.
Period Title: Overall Study
STARTED	27	26
COMPLETED	14	15
NOT COMPLETED	13	11

Baseline Characteristics

Arm/Group Title	Sodium Chloride	Sterile Water	Total
Arm/Group Description	Sodium chloride 1 meq/kg (0.4 ml/kg of 2.5meq/ml formulation for injection)q6hrs on days of life 7-35. Intervention was given enterally if feedings were at least 100 ml/kg/day; otherwise medication was diluted in equal amounts of dextrose 5% water and administered intravenously. Sodium chloride	Sterile water, 0.4 ml/kg q6hrs on days of life 7-35. Placebo is given enterally when infant is tolerating at least 100 ml/kg/day; otherwise the product is diluted in equal amounts of dextrose 5% water and administered intravenously. Placebo: sterile water, 0.4 ml/kg every 6 hours on days of life 7-35.	Total of all reporting groups
Overall Participants	27	26	53
Age (weeks) [Median (Full Range) ]
Median (Full Range) [weeks]	28.4	29.3	28.5
Sex: Female, Male (Count of Participants)
Female	14 51.9%	15 57.7%	29 54.7%
Male	13 48.1%	11 42.3%	24 45.3%
Weight at birth in grams (grams) [Median (Full Range) ]
Median (Full Range) [grams]	1080	1021	1051
Body length at birth in centimeters (centimeters) [Median (Full Range) ]
Median (Full Range) [centimeters]	35.8	34.9	35.4
Head circumference at birth in centimeters (centimeters) [Median (Full Range) ]
Median (Full Range) [centimeters]	25.1	24.6	24.9
Modified CRIB score (units on a scale) [Median (Full Range) ]
Median (Full Range) [units on a scale]	1	2	1
Maternal Milk as Primary Diet (participants) [Number]
Number [participants]	17 63%	14 53.8%	31 58.5%

Outcome Measures

1. Primary Outcome

Title	Weight Gain at Six Weeks of Age
Description	Average weight gain in g/kg/day and also as a % birthweight over the first six weeks of the study will be compared between the two study arms
Time Frame	Six weeks of age

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Placebo
Arm/Group Description	Sodium chloride 1 meq/kg (0.4 ml/kg of 2.5meq/ml formulation for injection)q6hrs on days of life 7-35. Intervention was given enterally if feedings were at least 100 ml/kg/day; otherwise medication was diluted in equal amounts of dextrose 5% water and administered intravenously. Sodium chloride	Sterile water, 0.4 ml/kg q6hrs on days of life 7-35. Placebo is given enterally when infant is tolerating at least 100 ml/kg/day; otherwise the product is diluted in equal amounts of dextrose 5% water and administered intravenously. Placebo: sterile water, 0.4 ml/kg every 6 hours on days of life 7-35.
Measure Participants	14	15
Median (Inter-Quartile Range) [g/kg/day]	26.9	22.4

2. Secondary Outcome

Title	Body Length at Six Weeks of Age
Description	The percentage of infants maintaining birth percentile at six weeks between the two study arms will be analyzed
Time Frame	six weeks of age

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Placebo
Arm/Group Description	Sodium chloride 1 meq/kg (0.4 ml/kg of 2.5meq/ml formulation for injection)q6hrs on days of life 7-35. Intervention was given enterally if feedings were at least 100 ml/kg/day; otherwise medication was diluted in equal amounts of dextrose 5% water and administered intravenously. Sodium chloride	Sterile water, 0.4 ml/kg q6hrs on days of life 7-35. Placebo is given enterally when infant is tolerating at least 100 ml/kg/day; otherwise the product is diluted in equal amounts of dextrose 5% water and administered intravenously. Placebo: sterile water, 0.4 ml/kg every 6 hours on days of life 7-35.
Measure Participants	14	15
Number [percentage]	14	15

3. Secondary Outcome

Title	Head Circumference
Description	The percentage of infants maintaining birth percentile for head circumference will be compared between the two groups.
Time Frame	six weeks of age

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Placebo
Arm/Group Description	Sodium chloride 1 meq/kg (0.4 ml/kg of 2.5meq/ml formulation for injection)q6hrs on days of life 7-35. Intervention was given enterally if feedings were at least 100 ml/kg/day; otherwise medication was diluted in equal amounts of dextrose 5% water and administered intravenously. Sodium chloride	Sterile water, 0.4 ml/kg q6hrs on days of life 7-35. Placebo is given enterally when infant is tolerating at least 100 ml/kg/day; otherwise the product is diluted in equal amounts of dextrose 5% water and administered intravenously. Placebo: sterile water, 0.4 ml/kg every 6 hours on days of life 7-35.
Measure Participants	14	15
Number [percent]	14	15

4. Secondary Outcome

Title	Mean Systolic Blood Pressure
Description	Systolic blood pressures at 36 weeks post-conceptual age will be compared between the two groups
Time Frame	36 weeks post-conceptual age

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Placebo
Arm/Group Description	Sodium chloride 1 meq/kg (0.4 ml/kg of 2.5meq/ml formulation for injection)q6hrs on days of life 7-35. Intervention was given enterally if feedings were at least 100 ml/kg/day; otherwise medication was diluted in equal amounts of dextrose 5% water and administered intravenously. Sodium chloride	Sterile water, 0.4 ml/kg q6hrs on days of life 7-35. Placebo is given enterally when infant is tolerating at least 100 ml/kg/day; otherwise the product is diluted in equal amounts of dextrose 5% water and administered intravenously. Placebo: sterile water, 0.4 ml/kg every 6 hours on days of life 7-35.
Measure Participants	14	15
Mean (Full Range) [mmHg]	84.4	81.8

5. Secondary Outcome

Title	Chronic Diuretic Therapy
Description	The incidence of chronic diuretic therapy will be compared between the two groups
Time Frame	patients will be followed during birth hospital stay; an expected average of 3 months of age

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Placebo
Arm/Group Description	Sodium chloride 1 meq/kg (0.4 ml/kg of 2.5meq/ml formulation for injection)q6hrs on days of life 7-35. Intervention was given enterally if feedings were at least 100 ml/kg/day; otherwise medication was diluted in equal amounts of dextrose 5% water and administered intravenously. Sodium chloride	Sterile water, 0.4 ml/kg q6hrs on days of life 7-35. Placebo is given enterally when infant is tolerating at least 100 ml/kg/day; otherwise the product is diluted in equal amounts of dextrose 5% water and administered intravenously. Placebo: sterile water, 0.4 ml/kg every 6 hours on days of life 7-35.
Measure Participants	14	15
Number [participants]	4 14.8%	3 11.5%

6. Secondary Outcome

Title	Late-onset Sepsis
Description	The incidence of late-onset sepsis, defined as positive blood culture for credible pathogen and/or 5 days of continuous antimicrobial therapy after the first week of life will be compared between the two groups.
Time Frame	patients will be followed during birth hospitalization; an expected average of 3 months of age

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Placebo
Arm/Group Description	Sodium chloride 1 meq/kg (0.4 ml/kg of 2.5meq/ml formulation for injection)q6hrs on days of life 7-35. Intervention was given enterally if feedings were at least 100 ml/kg/day; otherwise medication was diluted in equal amounts of dextrose 5% water and administered intravenously. Sodium chloride	Sterile water, 0.4 ml/kg q6hrs on days of life 7-35. Placebo is given enterally when infant is tolerating at least 100 ml/kg/day; otherwise the product is diluted in equal amounts of dextrose 5% water and administered intravenously. Placebo: sterile water, 0.4 ml/kg every 6 hours on days of life 7-35.
Measure Participants	27	26
Number [participants]	2 7.4%	12 46.2%

7. Secondary Outcome

Title	Necrotizing Enterocolitis
Description	The incidence of Bell stage II or greater necrotizing enterocolitis after the second week of life will be compared between the two groups
Time Frame	patients will be followed during birth hospitalization; an expected average of 3 months of age

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Placebo
Arm/Group Description	Sodium chloride 1 meq/kg (0.4 ml/kg of 2.5meq/ml formulation for injection)q6hrs on days of life 7-35. Intervention was given enterally if feedings were at least 100 ml/kg/day; otherwise medication was diluted in equal amounts of dextrose 5% water and administered intravenously. Sodium chloride	Sterile water, 0.4 ml/kg q6hrs on days of life 7-35. Placebo is given enterally when infant is tolerating at least 100 ml/kg/day; otherwise the product is diluted in equal amounts of dextrose 5% water and administered intravenously. Placebo: sterile water, 0.4 ml/kg every 6 hours on days of life 7-35.
Measure Participants	27	26
Number [participants]	0 0%	4 15.4%

8. Secondary Outcome

Title	Chronic Lung Disease
Description	The incidence of chronic lung disease, defined as respiratory support at 36 weeks postmenstrual age will be compared between the two groups
Time Frame	36 weeks post-mentrual age

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Placebo
Arm/Group Description	Sodium chloride 1 meq/kg (0.4 ml/kg of 2.5meq/ml formulation for injection)q6hrs on days of life 7-35. Intervention was given enterally if feedings were at least 100 ml/kg/day; otherwise medication was diluted in equal amounts of dextrose 5% water and administered intravenously. Sodium chloride	Sterile water, 0.4 ml/kg q6hrs on days of life 7-35. Placebo is given enterally when infant is tolerating at least 100 ml/kg/day; otherwise the product is diluted in equal amounts of dextrose 5% water and administered intravenously. Placebo: sterile water, 0.4 ml/kg every 6 hours on days of life 7-35.
Measure Participants	27	26
Number [participants]	9 33.3%	5 19.2%

9. Secondary Outcome

Title	Mortality
Description	The incidence of death during birth hospitalization will be compared between the two study arms
Time Frame	patients will be followed during birth hospitalization; an expected 3 months of age

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Placebo
Arm/Group Description	Sodium chloride 1 meq/kg (0.4 ml/kg of 2.5meq/ml formulation for injection)q6hrs on days of life 7-35. Intervention was given enterally if feedings were at least 100 ml/kg/day; otherwise medication was diluted in equal amounts of dextrose 5% water and administered intravenously. Sodium chloride	Sterile water, 0.4 ml/kg q6hrs on days of life 7-35. Placebo is given enterally when infant is tolerating at least 100 ml/kg/day; otherwise the product is diluted in equal amounts of dextrose 5% water and administered intravenously. Placebo: sterile water, 0.4 ml/kg every 6 hours on days of life 7-35.
Measure Participants	27	26
Number [participants]	0 0%	4 15.4%

10. Secondary Outcome

Title	Patent Ductus Arteriosus
Description	prolonged Patent Ductus Arteriosus after the second week of life
Time Frame	After the second week of life

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention	Placebo
Arm/Group Description	Sodium chloride 1 meq/kg (0.4 ml/kg of 2.5meq/ml formulation for injection)q6hrs on days of life 7-35. Intervention was given enterally if feedings were at least 100 ml/kg/day; otherwise medication was diluted in equal amounts of dextrose 5% water and administered intravenously. Sodium chloride	Sterile water, 0.4 ml/kg q6hrs on days of life 7-35. Placebo is given enterally when infant is tolerating at least 100 ml/kg/day; otherwise the product is diluted in equal amounts of dextrose 5% water and administered intravenously. Placebo: sterile water, 0.4 ml/kg every 6 hours on days of life 7-35.
Measure Participants	27	26
Number [participants]	7 25.9%	9 34.6%

Adverse Events

Arm/Group Title	Intervention		Placebo
Arm/Group Description	Sodium chloride 1 meq/kg (0.4 ml/kg of 2.5meq/ml formulation for injection)q6hrs on days of life 7-35. Intervention was given enterally if feedings were at least 100 ml/kg/day; otherwise medication was diluted in equal amounts of dextrose 5% water and administered intravenously. Sodium chloride		Sterile water, 0.4 ml/kg q6hrs on days of life 7-35. Placebo is given enterally when infant is tolerating at least 100 ml/kg/day; otherwise the product is diluted in equal amounts of dextrose 5% water and administered intravenously. Placebo: sterile water, 0.4 ml/kg every 6 hours on days of life 7-35.
All Cause Mortality
	Intervention		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Intervention		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Intervention		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/27 (11.1%)		0/26 (0%)
Metabolism and nutrition disorders
hypernatremia	3/27 (11.1%)		0/26 (0%)

Limitations/Caveats

Study was terminated after 95% of sample size was recruited. Small number of subjects are analyzed.

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.