Multi-dose Pharmacokinetics and Dose Ranging of Inositol in Premature Infants (INS-2)
Sponsor
NICHD Neonatal Research Network (Other)
Overall Status
Completed
CT.gov ID
NCT01030575
Collaborator
National Eye Institute (NEI) (NIH), National Center for Research Resources (NCRR) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
125
17
4
44
7.4
0.2
Study Details
Study Description
Brief Summary
This pilot study is a randomized, placebo-controlled, clinical trial to measure changes in blood and urine levels of inositol in premature infants at high risk for retinopathy of prematurity (ROP) following repeated doses of inositol. Based on previous studies, the premise is that maintaining inositol concentrations similar to those occurring naturally in utero will reduce the rates of ROP and bronchopulmonary dysplasia in premature infants. The objective is to evaluate pharmacokinetics, safety, and clinical outcomes of multiple doses of three different dose amounts of myo-inositol (provided by Abbott Laboratories) in very low birth weight premature infants. This study will enroll an estimated 96 infants at 17 NICHD Neonatal Research Network sites. Infants will be randomly assigned to receive either 10 mg/kg of 5% inositol, 40 mg/kg of 5% inositol, 80 mg/kg of 5% inositol, or 5% glucose given in the same volumes and timings as the inositol dosage to maintain masking. Enrollees will receive their assigned dose or placebo daily, starting within 72 hours of birth, and continuing until they reach 34 weeks post-menstrual age, 10 weeks chronologic age, or until the time of hospital discharge, whichever occurs first. The study drug will be administered first intravenously; as the infants progress to full feeding, the drug will be given enterally (orally or via feeding tube). Enrollees will be seen for a follow-up examination at 18-22 months corrected age. This pilot study is in preparation for a future Phase III multi-center randomized controlled trial.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Retinopathy of prematurity (ROP) is an abnormal growth of the blood vessels in the eye that occurs primarily in very premature infants. Eye development occurs normally in the womb; in infants born prematurely, however, the blood vessels must finish developing outside the protective environment of the uterus. Retinopathy of prematurity (also known as retrolental fibroplasia) is a leading cause of blindness and other vision impairments (myopia, strabismus, and amblyopia) in children, both in developed and developing countries.
Inositol is a naturally-occurring sugar alcohol produced by the fetus and placenta and is present in high levels in fetal blood throughout pregnancy in humans and other animals. Serum levels fall rapidly after birth, although this fall is moderated in infants who receive breast milk or fortified formula. Two randomized trials have shown that intravenous inositol supplementation in the first week significantly reduced death, bronchopulmonary dysplasia (BPD), and retinopathy. One study of enteral supplements (given orally or via feeding tube) was less convincing, but also supported reduction of retinopathy.
This pilot study will evaluate changes in blood and urine inositol levels (half-life pharmacokinetics) of multiple doses of myo-inositol (provided by Abbott Laboratories, Abbott Nutrition Division) given to very low birth weight infants. The premise is that maintaining inositol concentrations similar to those occurring naturally in utero will reduce the rates of retinopathy and bronchopulmonary dysplasia in premature infants. Results from this study will be used to select the dose for a large multi-center trial.
In this study, 17 NICHD Neonatal Research Network sites will enroll approximately 96 infants at 12-72 hours of age. Enrolled infants will be randomly assigned to receive either 10mg/kg of 5% inositol, 40 mg/kg of 5% inositol, 80 mg/kg of 5% inositol, or 5% glucose given in the same volumes and timings as the inositol dosage to maintain masking. Inositol will be administered intravenously until babies are feeding normally, at which time the same dose and formulation will be administered enterally (orally or via feeding tube). Concentrations of inositol will be measured in blood, urine, and milk received.
Stratification: Recruitment will be stratified by gestational age into infants born at 23 0/7 to 26 6/7 weeks gestational age and infants born at 27 0/7 to 29 6/7 weeks gestational age.
Study Design
Study Type:
Interventional
Actual Enrollment
:
125 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Phase II Randomized, Double-Masked, Placebo-Controlled, Safety, Pharmacokinetic, and Dose-Ranging Study of Multiple Doses of Inositol in Premature Infants
Study Start Date
:
Jan 1, 2010
Actual Primary Completion Date
:
May 1, 2011
Actual Study Completion Date
:
Sep 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Inositol low volume 10 mg/kg/day Intravenous inositol 5% |
Drug: Inositol lower volume
5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes
Other Names:
|
| Experimental: Inositol mid-level volume 40 mg/kg/day Intravenous inositol 5% |
Drug: Inositol mid-level volume
20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes
Other Names:
|
| Experimental: Inositol high volume 80 mg/kg/day Intravenous inositol 5% |
Drug: Inositol high volume
40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes
Other Names:
|
| Placebo Comparator: Placebo Glucose 5% given in volumes equal to that of the comparator drug |
Drug: Placebo low volume
Glucose 5% given in volumes equal to that of the comparator drug
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Population Pharmacokinetics: V - Volume [8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.]
- Population Pharmacokinetics: Cl - Clearance [8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.]
- Population Pharmacokinetics: R - Endogenous Infusion Rate [8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.]
- Population Pharmacokinetics: k - Elimination Rate (Cl/V) [8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.]
- Population Pharmacokinetics: t1/2 - Half-Life (0.693/k) [8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.]
- Population Pharmacokinetics: E - Concentration Due to Endogenous Infusion (R/Cl) [8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.]
- SD of Residual Error (mg/l) [8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70.]
Secondary Outcome Measures
- Number of Participants With Any Retinopathy of Prematurity (ROP) [18-22 month corrected age]
Any ROP is defined as ROP of any severity that is observed at 18-22 month corrected age
- Number of Participants With Any Retinopathy of Prematurity Through 18-22 Month Corrected Age or Death [18-22 month corrected age]
Number of participants with any Retinopathy of Prematurity (ROP) through 18-22 month corrected age or death
- Number of Participants With Any Ophthalmologic Diagnosis [18-22 month corrected age]
Any ophthalmologic diagnosis at 18-22 month corrected age
- Number of Participants With Any Ophthalmologic Treatment [18-22 month corrected age]
Any ophthalmologic treatment at 18-22 month corrected age
- Number of Participants With Any Ophthalmologic Surgical Treatment [18-22 month corrected age]
Any ophthalmologic surgical treatment at 18-22 month corrected age
- Number of Participants With Any Ophthalmologic Medical Treatment [18-22 month corrected age]
Any ophthalmologic medical treatment at 18-22 month corrected age
- Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age [18-22 month corrected age]
A composite outcome that measures the occurrence of neurodevelopmental impairment between birth and 18-22 months corrected age.
- Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age or Death [8-22 months corrected age.]
Moderate or Severe NDI defined as occurrence of any of the following: GMFCS level II or higher (severe is level 4 or 5), Bayley III cognitive composite score < 85 (severe is <70), Bayley III motor composite score < 85 (severe is <70), unilateral blind or bilateral blind, permanent hearing loss that does not permit child to understand directions of the examiner and communicate despite amplification with cochlear implant or hearing aid
- Number of Participants With Moderate or Severe Cerebral Palsy [18-22 months corrected age.]
Cerebral palsy by severity category (absent/mild/moderate/severe).
- Number of Participants With Composite Motor Score Less Than 70 [18-22 months corrected age]
This is measured as a scored of less than 70 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite motor score. Higher scores indicate better performance.
- Number of Participants With Composite Cognitive Score Less Than 70 [18-22 months corrected age.]
This is measured as a score of less than 70 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite cognitive score
- Number of Participants With Severe Hearing Impairment [18-22 months corrected age.]
Defined as permanent hearing loss that does not permit child to understand directions of the examiner and communicate despite amplification with cochlear implant or hearing aid.
- Number of Participants With Severe Vision Loss [18-22 Months Corrected Age]
Vision loss as diagnosed by an ophthalmologist as legally blind, and subdivided into "ophthalmic origin", or "not ophthalmic origin" (i.e., cortical blindness is non-ophthalmic in origin and indicates that there is no retinal detachment or other abnormal fundus or ocular finding, except optic atrophy. Such cases will be considered central [neurologic] in origin.)
- Number of Participants With Gross Motor Function Greater Than or Equal to 2 [18 -22 months corrected age]
A Gross Motor Function Classification System (GMFCS) level of at least II (on a scale from level I to V, with I indicating normal gross motor function and higher levels indicating greater impairment). Level II is defined as Infants maintain floor sitting but may need to use their hands for support to maintain balance. Infants creep on their stomach or crawl on hands and knees with reciprocal leg movement. Infants may pull to stand and take steps holding on to furniture.)
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Hours
to 72 Hours
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
23 0/7 to 26 6/7 weeks gestational age (48 infants) or
-
27 0/7 to 29 6/7 weeks gestational age (48 infants)
-
401 grams birth weight or larger
-
12-72 hours of age
Exclusion Criteria:
-
Major congenital and intracranial anomalies
-
Moribund or not to be provided continued support
-
Seizures
-
Suspected renal failure (oliguria <0.6 cc/kg/hr for >24 hours or creatinine >2.5 mg/dL)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35233 |
| 2 | Stanford University | Palo Alto | California | United States | 94304 |
| 3 | Yale University | New Haven | Connecticut | United States | 06504 |
| 4 | Emory University | Atlanta | Georgia | United States | 30303 |
| 5 | Indiana University | Indianapolis | Indiana | United States | 46202 |
| 6 | University of Iowa | Iowa City | Iowa | United States | 52242 |
| 7 | Tufts Medical Center | Boston | Massachusetts | United States | 02111 |
| 8 | Wayne State University | Detroit | Michigan | United States | 48201 |
| 9 | University of New Mexico | Albuquerque | New Mexico | United States | 87131 |
| 10 | University of Rochester | Rochester | New York | United States | 14642 |
| 11 | RTI International | Durham | North Carolina | United States | 27705 |
| 12 | Duke University | Durham | North Carolina | United States | 27710 |
| 13 | Case Western Reserve University, Rainbow Babies and Children's Hospital | Cleveland | Ohio | United States | 44106 |
| 14 | Brown University, Women & Infants Hospital of Rhode Island | Providence | Rhode Island | United States | 02905 |
| 15 | University of Texas Southwestern Medical Center at Dallas | Dallas | Texas | United States | 75235 |
| 16 | University of Texas Health Science Center at Houston | Houston | Texas | United States | 77030 |
| 17 | University of Utah | Salt Lake City | Utah | United States | 84108 |
Sponsors and Collaborators
- NICHD Neonatal Research Network
- National Eye Institute (NEI)
- National Center for Research Resources (NCRR)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
- Principal Investigator: Abbot R. Laptook, MD, Brown University, Women & Infants Hospital of Rhode Island
- Principal Investigator: Michele C. Walsh, MD MS, Case Western Reserve University, Rainbow Babies and Children's Hospital
- Principal Investigator: Ronald N. Goldberg, MD, Duke University
- Principal Investigator: Barbara J. Stoll, MD, Emory University
- Principal Investigator: Brenda B. Poindexter, MD MS, Indiana University
- Principal Investigator: Abhik Das, PhD, RTI International
- Principal Investigator: Krisa P. Van Meurs, MD, Stanford University
- Principal Investigator: Ivan D. Frantz III, MD, Tufts Medical Center
- Principal Investigator: Kurt Schibler, MD, Children's Hospital Medical Center, Cincinnati
- Principal Investigator: Waldemar A. Carlo, MD, University of Alabama at Birmingham
- Principal Investigator: Edward F Bell, MD, University of Iowa
- Principal Investigator: Kristi L. Watterberg, MD, University of New Mexico
- Principal Investigator: Dale L. Phelps, MD, University of Rochester
- Principal Investigator: Pablo J. Sanchez, MD, University of Texas, Southwestern Medical Center at Dallas
- Principal Investigator: Kathleen A. Kennedy, MD MPH, The University of Texas Health Science Center, Houston
- Principal Investigator: Roger G. Faix, MD, University of Utah
- Principal Investigator: Seetha Shankaran, MD, Wayne State University
- Principal Investigator: Richard A. Ehrenkranz, MD, Yale University
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
NICHD Neonatal Research Network
ClinicalTrials.gov Identifier:
NCT01030575
Other Study ID Numbers:
- NICHD-NRN-0036-2
- U10HD021364
- U10HD021373
- U10HD021385
- U10HD027851
- U10HD027853
- U10HD027856
- U10HD027871
- U10HD027880
- U10HD027904
- U10HD034216
- U10HD036790
- U10HD040492
- U10HD040689
- U10HD053089
- U10HD053109
- U10HD053119
- U10HD053124
- UL1RR024139
- UL1RR025744
- UL1RR024979
- M01RR008084
First Posted:
Dec 11, 2009
Last Update Posted:
Jun 14, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by NICHD Neonatal Research Network
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Infants who were 23(0/7) to 29(6/7) weeks gestational age, weighed at least 400grams, survived >12 hours, and could receive study drug by 72 hours after birth were screened and enrolled (after meeting eligibility criteria) across 14 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN) |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo |
|---|---|---|---|---|
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug |
| Period Title: Overall Study | ||||
| STARTED | 29 | 30 | 28 | 35 |
| COMPLETED | 29 | 30 | 28 | 35 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug | Total of all reporting groups |
| Overall Participants | 29 | 30 | 28 | 35 | 122 |
| Age (weeks) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [weeks] |
26.6
(1.8)
|
26.7
(1.8)
|
26.7
(1.9)
|
26.5
(1.6)
|
26.6
(1.7)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
15
51.7%
|
14
46.7%
|
16
57.1%
|
17
48.6%
|
62
50.8%
|
| Male |
14
48.3%
|
16
53.3%
|
12
42.9%
|
18
51.4%
|
60
49.2%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
3
10.3%
|
7
23.3%
|
8
28.6%
|
9
25.7%
|
27
22.1%
|
| Not Hispanic or Latino |
26
89.7%
|
23
76.7%
|
20
71.4%
|
26
74.3%
|
95
77.9%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
3
10.3%
|
0
0%
|
0
0%
|
0
0%
|
3
2.5%
|
| Asian |
1
3.4%
|
1
3.3%
|
0
0%
|
0
0%
|
2
1.6%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
15
51.7%
|
12
40%
|
13
46.4%
|
18
51.4%
|
58
47.5%
|
| White |
9
31%
|
17
56.7%
|
15
53.6%
|
17
48.6%
|
58
47.5%
|
| More than one race |
1
3.4%
|
0
0%
|
0
0%
|
0
0%
|
1
0.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Head Circumference (cm) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [cm] |
24.1
(2.0)
|
25.1
(2.5)
|
24.6
(1.9)
|
23.8
(2.0)
|
24.3
(2.1)
|
| Birth Weight (grams) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [grams] |
897
(272)
|
939
(245)
|
921
(286)
|
884
(224)
|
909
(253)
|
| Antenatal Steroids (Count of Participants) | |||||
| Yes |
24
82.8%
|
24
80%
|
26
92.9%
|
32
91.4%
|
106
86.9%
|
| No |
5
17.2%
|
6
20%
|
2
7.1%
|
3
8.6%
|
16
13.1%
|
| Early Onset Sepsis (Count of Participants) | |||||
| Yes |
0
0%
|
1
3.3%
|
0
0%
|
0
0%
|
1
0.8%
|
| No |
29
100%
|
29
96.7%
|
28
100%
|
35
100%
|
121
99.2%
|
| Cesarean Delivery (Count of Participants) | |||||
| Yes |
16
55.2%
|
19
63.3%
|
14
50%
|
21
60%
|
70
57.4%
|
| No |
13
44.8%
|
11
36.7%
|
14
50%
|
14
40%
|
52
42.6%
|
| Chorioamnionitis (Count of Participants) | |||||
| Yes |
4
13.8%
|
4
13.3%
|
3
10.7%
|
5
14.3%
|
16
13.1%
|
| No |
25
86.2%
|
26
86.7%
|
25
89.3%
|
30
85.7%
|
106
86.9%
|
| APGAR 1-minute (units on a scale) [Median (Full Range) ] | |||||
| Median (Full Range) [units on a scale] |
5
|
3
|
5
|
3
|
4
|
| APGAR 5-minute (units on a scale) [Median (Full Range) ] | |||||
| Median (Full Range) [units on a scale] |
8
|
7
|
7
|
7
|
7
|
| Gestational Age (GA) STRATUM (Count of Participants) | |||||
| 23-26 Weeks |
15
51.7%
|
16
53.3%
|
14
50%
|
19
54.3%
|
64
52.5%
|
| 27-29 Weeks |
14
48.3%
|
14
46.7%
|
14
50%
|
16
45.7%
|
58
47.5%
|
Outcome Measures
| Title | Population Pharmacokinetics: V - Volume |
|---|---|
| Description | |
| Time Frame | 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All 4 arms of the study are used in the Pop-PK analysis population. 1 infant randomized to the placebo arm incorrectly received the low dose. The infant was included in the low dose arm for the pharmacokinetics analyses and as randomized to the placebo arm for all other analyzes. |
| Arm/Group Title | PK Population |
|---|---|
| Arm/Group Description | A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model. |
| Measure Participants | 122 |
| Mean (Standard Error) [l/kg] |
0.6572
(0.0707)
|
| Title | Population Pharmacokinetics: Cl - Clearance |
|---|---|
| Description | |
| Time Frame | 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All 4 arms of the study are used in the Pop-PK analysis population. 1 infant randomized to the placebo arm incorrectly received the low dose. The infant was included in the low dose arm for the pharmacokinetics analyses and as randomized to the placebo arm for all other analyzes. |
| Arm/Group Title | PK Population |
|---|---|
| Arm/Group Description | A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model. |
| Measure Participants | 122 |
| Mean (Standard Error) [(l/kg)/h] |
0.0577
(0.0061)
|
| Title | Population Pharmacokinetics: R - Endogenous Infusion Rate |
|---|---|
| Description | |
| Time Frame | 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All 4 arms of the study are used in the Pop-PK analysis population. 1 infant randomized to the placebo arm incorrectly received the low dose. The infant was included in the low dose arm for the pharmacokinetics analyses and as randomized to the placebo arm for all other analyzes. |
| Arm/Group Title | PK Population |
|---|---|
| Arm/Group Description | A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model. |
| Measure Participants | 122 |
| Mean (Standard Error) [(mg/kg)/h] |
2.369
(0.3151)
|
| Title | Population Pharmacokinetics: k - Elimination Rate (Cl/V) |
|---|---|
| Description | |
| Time Frame | 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All 4 arms of the study are used in the Pop-PK analysis population. 1 infant randomized to the placebo arm incorrectly received the low dose. The infant was included in the low dose arm for the pharmacokinetics analyses and as randomized to the placebo arm for all other analyzes. |
| Arm/Group Title | PK Population |
|---|---|
| Arm/Group Description | A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model. |
| Measure Participants | 122 |
| Mean (Standard Error) [liter/hour] |
0.0878
(0.0137)
|
| Title | Population Pharmacokinetics: t1/2 - Half-Life (0.693/k) |
|---|---|
| Description | |
| Time Frame | 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All 4 arms of the study are used in the Pop-PK analysis population. 1 infant randomized to the placebo arm incorrectly received the low dose. The infant was included in the low dose arm for the pharmacokinetics analyses and as randomized to the placebo arm for all other analyzes. |
| Arm/Group Title | PK Population |
|---|---|
| Arm/Group Description | A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model. |
| Measure Participants | 122 |
| Mean (Standard Error) [hour] |
7.90
(1.229)
|
| Title | Population Pharmacokinetics: E - Concentration Due to Endogenous Infusion (R/Cl) |
|---|---|
| Description | |
| Time Frame | 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All 4 arms of the study are used in the Pop-PK analysis population. 1 infant randomized to the placebo arm incorrectly received the low dose. The infant was included in the low dose arm for the pharmacokinetics analyses and as randomized to the placebo arm for all other analyzes. |
| Arm/Group Title | PK Population |
|---|---|
| Arm/Group Description | A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model. |
| Measure Participants | 122 |
| Mean (Standard Error) [miligrams/liter] |
41.06
(1.777)
|
| Title | SD of Residual Error (mg/l) |
|---|---|
| Description | |
| Time Frame | 8-10 blood samples per infant were drawn over 10 weeks for infant safety with the full study duration represented across all infants. Samples were drawn at baseline & on days 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 35, 42, 56, and 70. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All 4 arms of the study are used in the Pop-PK analysis population. 1 infant randomized to the placebo arm incorrectly received the low dose. The infant was included in the low dose arm for the pharmacokinetics analyses and as randomized to the placebo arm for all other analyzes. |
| Arm/Group Title | PK Population |
|---|---|
| Arm/Group Description | A population pharmacokinetics (Pop-PK) model was used to combine the serum inositol concentrations measured at the sparse sampling time points described under Time Frame. A 1-compartment multiple-administration intravenous infusion model with linear elimination and an added term for a steady state infusion rate of inositol from feeding and endogenous synthesis. The model is used to estimate typical (fixed effect) values of volume of distribution (V), clearance (Cl) and endogenous infusion rate (R). It is not possible to include separate estimates of the Pop-PK parameters by arm since the same values are used across all arms combined with the dosage of inositol received by an infant applied separately in the Pop-PK model. |
| Measure Participants | 122 |
| Mean (Standard Error) [mg/l] |
24.77
(0.971)
|
| Title | Number of Participants With Any Retinopathy of Prematurity (ROP) |
|---|---|
| Description | Any ROP is defined as ROP of any severity that is observed at 18-22 month corrected age |
| Time Frame | 18-22 month corrected age |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo |
|---|---|---|---|---|
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug |
| Measure Participants | 24 | 23 | 25 | 24 |
| Count of Participants [Participants] |
11
37.9%
|
11
36.7%
|
14
50%
|
12
34.3%
|
| Title | Number of Participants With Any Retinopathy of Prematurity Through 18-22 Month Corrected Age or Death |
|---|---|
| Description | Number of participants with any Retinopathy of Prematurity (ROP) through 18-22 month corrected age or death |
| Time Frame | 18-22 month corrected age |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo |
|---|---|---|---|---|
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug |
| Measure Participants | 26 | 29 | 26 | 30 |
| Count of Participants [Participants] |
13
44.8%
|
17
56.7%
|
15
53.6%
|
18
51.4%
|
| Title | Number of Participants With Any Ophthalmologic Diagnosis |
|---|---|
| Description | Any ophthalmologic diagnosis at 18-22 month corrected age |
| Time Frame | 18-22 month corrected age |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo |
|---|---|---|---|---|
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug |
| Measure Participants | 24 | 21 | 22 | 21 |
| Count of Participants [Participants] |
9
31%
|
6
20%
|
10
35.7%
|
5
14.3%
|
| Title | Number of Participants With Any Ophthalmologic Treatment |
|---|---|
| Description | Any ophthalmologic treatment at 18-22 month corrected age |
| Time Frame | 18-22 month corrected age |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo |
|---|---|---|---|---|
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug |
| Measure Participants | 24 | 21 | 22 | 21 |
| Count of Participants [Participants] |
4
13.8%
|
4
13.3%
|
2
7.1%
|
5
14.3%
|
| Title | Number of Participants With Any Ophthalmologic Surgical Treatment |
|---|---|
| Description | Any ophthalmologic surgical treatment at 18-22 month corrected age |
| Time Frame | 18-22 month corrected age |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo |
|---|---|---|---|---|
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug |
| Measure Participants | 24 | 21 | 22 | 21 |
| Count of Participants [Participants] |
3
10.3%
|
4
13.3%
|
0
0%
|
4
11.4%
|
| Title | Number of Participants With Any Ophthalmologic Medical Treatment |
|---|---|
| Description | Any ophthalmologic medical treatment at 18-22 month corrected age |
| Time Frame | 18-22 month corrected age |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo |
|---|---|---|---|---|
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug |
| Measure Participants | 24 | 21 | 22 | 21 |
| Count of Participants [Participants] |
2
6.9%
|
1
3.3%
|
1
3.6%
|
2
5.7%
|
| Title | Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age |
|---|---|
| Description | A composite outcome that measures the occurrence of neurodevelopmental impairment between birth and 18-22 months corrected age. |
| Time Frame | 18-22 month corrected age |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo |
|---|---|---|---|---|
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug |
| Measure Participants | 24 | 23 | 22 | 27 |
| Count of Participants [Participants] |
8
27.6%
|
9
30%
|
11
39.3%
|
13
37.1%
|
| Title | Number of Participants With Moderate or Severe Neurodevelopmental Impairment at 18-22 Month Corrected Age or Death |
|---|---|
| Description | Moderate or Severe NDI defined as occurrence of any of the following: GMFCS level II or higher (severe is level 4 or 5), Bayley III cognitive composite score < 85 (severe is <70), Bayley III motor composite score < 85 (severe is <70), unilateral blind or bilateral blind, permanent hearing loss that does not permit child to understand directions of the examiner and communicate despite amplification with cochlear implant or hearing aid |
| Time Frame | 8-22 months corrected age. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo |
|---|---|---|---|---|
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug |
| Measure Participants | 26 | 29 | 24 | 34 |
| Count of Participants [Participants] |
10
34.5%
|
15
50%
|
13
46.4%
|
20
57.1%
|
| Title | Number of Participants With Moderate or Severe Cerebral Palsy |
|---|---|
| Description | Cerebral palsy by severity category (absent/mild/moderate/severe). |
| Time Frame | 18-22 months corrected age. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo |
|---|---|---|---|---|
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug |
| Measure Participants | 24 | 24 | 23 | 27 |
| Count of Participants [Participants] |
0
0%
|
1
3.3%
|
1
3.6%
|
2
5.7%
|
| Title | Number of Participants With Composite Motor Score Less Than 70 |
|---|---|
| Description | This is measured as a scored of less than 70 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite motor score. Higher scores indicate better performance. |
| Time Frame | 18-22 months corrected age |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo |
|---|---|---|---|---|
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug |
| Measure Participants | 24 | 22 | 22 | 25 |
| Count of Participants [Participants] |
1
3.4%
|
1
3.3%
|
2
7.1%
|
6
17.1%
|
| Title | Number of Participants With Composite Cognitive Score Less Than 70 |
|---|---|
| Description | This is measured as a score of less than 70 on the Bayley Scale of Infant and Toddler Development (BSID)-III composite cognitive score |
| Time Frame | 18-22 months corrected age. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo |
|---|---|---|---|---|
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug |
| Measure Participants | 24 | 23 | 22 | 26 |
| Count of Participants [Participants] |
0
0%
|
1
3.3%
|
1
3.6%
|
2
5.7%
|
| Title | Number of Participants With Severe Hearing Impairment |
|---|---|
| Description | Defined as permanent hearing loss that does not permit child to understand directions of the examiner and communicate despite amplification with cochlear implant or hearing aid. |
| Time Frame | 18-22 months corrected age. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to Treat (ITT) |
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo |
|---|---|---|---|---|
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug |
| Measure Participants | 24 | 24 | 23 | 27 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Severe Vision Loss |
|---|---|
| Description | Vision loss as diagnosed by an ophthalmologist as legally blind, and subdivided into "ophthalmic origin", or "not ophthalmic origin" (i.e., cortical blindness is non-ophthalmic in origin and indicates that there is no retinal detachment or other abnormal fundus or ocular finding, except optic atrophy. Such cases will be considered central [neurologic] in origin.) |
| Time Frame | 18-22 Months Corrected Age |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to Treat (ITT) |
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo |
|---|---|---|---|---|
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug |
| Measure Participants | 24 | 24 | 23 | 27 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Gross Motor Function Greater Than or Equal to 2 |
|---|---|
| Description | A Gross Motor Function Classification System (GMFCS) level of at least II (on a scale from level I to V, with I indicating normal gross motor function and higher levels indicating greater impairment). Level II is defined as Infants maintain floor sitting but may need to use their hands for support to maintain balance. Infants creep on their stomach or crawl on hands and knees with reciprocal leg movement. Infants may pull to stand and take steps holding on to furniture.) |
| Time Frame | 18 -22 months corrected age |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo |
|---|---|---|---|---|
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug |
| Measure Participants | 24 | 24 | 23 | 27 |
| Count of Participants [Participants] |
0
0%
|
2
6.7%
|
3
10.7%
|
4
11.4%
|
Adverse Events
| Time Frame | From start of study drug treatment through 7-days post last dose of study drug | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Note that the primary trial publication mislabels serious adverse events as severe adverse events. | |||||||
| Arm/Group Title | Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo | ||||
| Arm/Group Description | 10 mg/kg/day Intravenous inositol 5% Inositol lower volume: 5 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 40 mg/kg/day Intravenous inositol 5% Inositol mid-level volume: 20 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | 80 mg/kg/day Intravenous inositol 5% Inositol high volume: 40 mg/kg/dose inositol every 12 hours, given intravenously over 20 minutes | Glucose 5% given in volumes equal to that of the comparator drug Placebo low volume: Glucose 5% given in volumes equal to that of the comparator drug | ||||
All Cause Mortality |
||||||||
| Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/29 (6.9%) | 5/30 (16.7%) | 1/28 (3.6%) | 6/35 (17.1%) | ||||
Serious Adverse Events |
||||||||
| Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/29 (58.6%) | 20/30 (66.7%) | 17/28 (60.7%) | 28/35 (80%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anemia | 5/29 (17.2%) | 6/30 (20%) | 7/28 (25%) | 13/35 (37.1%) | ||||
| Thrombocytosis | 4/29 (13.8%) | 1/30 (3.3%) | 2/28 (7.1%) | 5/35 (14.3%) | ||||
| Cardiac disorders | ||||||||
| Poor perfusion or hypotension | 5/29 (17.2%) | 3/30 (10%) | 6/28 (21.4%) | 8/35 (22.9%) | ||||
| Gastrointestinal disorders | ||||||||
| Delayed gastric emptying | 3/29 (10.3%) | 7/30 (23.3%) | 5/28 (17.9%) | 7/35 (20%) | ||||
| Other | 3/29 (10.3%) | 0/30 (0%) | 2/28 (7.1%) | 4/35 (11.4%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hyperglycemia | 1/29 (3.4%) | 1/30 (3.3%) | 1/28 (3.6%) | 4/35 (11.4%) | ||||
| Renal and urinary disorders | ||||||||
| Other | 0/29 (0%) | 0/30 (0%) | 0/28 (0%) | 2/35 (5.7%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Apnea | 4/29 (13.8%) | 6/30 (20%) | 9/28 (32.1%) | 6/35 (17.1%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Inositol Low Volume | Inositol Mid-level Volume | Inositol High Volume | Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 24/29 (82.8%) | 20/30 (66.7%) | 19/28 (67.9%) | 24/35 (68.6%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anemia | 2/29 (6.9%) | 7/30 (23.3%) | 4/28 (14.3%) | 4/35 (11.4%) | ||||
| Neutropenia | 5/29 (17.2%) | 2/30 (6.7%) | 3/28 (10.7%) | 2/35 (5.7%) | ||||
| Thrombocytopenia | 3/29 (10.3%) | 2/30 (6.7%) | 1/28 (3.6%) | 1/35 (2.9%) | ||||
| Thrombocytosis | 5/29 (17.2%) | 3/30 (10%) | 4/28 (14.3%) | 6/35 (17.1%) | ||||
| Other | 1/29 (3.4%) | 0/30 (0%) | 0/28 (0%) | 1/35 (2.9%) | ||||
| Cardiac disorders | ||||||||
| Congestive heart failure | 0/29 (0%) | 1/30 (3.3%) | 0/28 (0%) | 0/35 (0%) | ||||
| Hypertension | 4/29 (13.8%) | 3/30 (10%) | 4/28 (14.3%) | 5/35 (14.3%) | ||||
| Poor perfusion or hypotension | 3/29 (10.3%) | 2/30 (6.7%) | 3/28 (10.7%) | 3/35 (8.6%) | ||||
| Tachycardia | 0/29 (0%) | 1/30 (3.3%) | 0/28 (0%) | 0/35 (0%) | ||||
| Other | 1/29 (3.4%) | 0/30 (0%) | 4/28 (14.3%) | 2/35 (5.7%) | ||||
| Gastrointestinal disorders | ||||||||
| Delayed gastric emptying | 10/29 (34.5%) | 8/30 (26.7%) | 7/28 (25%) | 10/35 (28.6%) | ||||
| Direct (conjugated) hyperbilirubinemia | 0/29 (0%) | 1/30 (3.3%) | 4/28 (14.3%) | 3/35 (8.6%) | ||||
| Elevated liver enzymes | 3/29 (10.3%) | 1/30 (3.3%) | 0/28 (0%) | 1/35 (2.9%) | ||||
| Emesis | 2/29 (6.9%) | 0/30 (0%) | 0/28 (0%) | 0/35 (0%) | ||||
| Other | 2/29 (6.9%) | 1/30 (3.3%) | 0/28 (0%) | 2/35 (5.7%) | ||||
| General disorders | ||||||||
| Other | 1/29 (3.4%) | 0/30 (0%) | 1/28 (3.6%) | 1/35 (2.9%) | ||||
| Fever | 0/29 (0%) | 0/30 (0%) | 0/28 (0%) | 1/35 (2.9%) | ||||
| Hypothermia | 0/29 (0%) | 0/30 (0%) | 1/28 (3.6%) | 0/35 (0%) | ||||
| Infections and infestations | ||||||||
| Infection | 2/29 (6.9%) | 0/30 (0%) | 1/28 (3.6%) | 1/35 (2.9%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hyperglycemia | 3/29 (10.3%) | 4/30 (13.3%) | 2/28 (7.1%) | 5/35 (14.3%) | ||||
| Hypoglycemia | 1/29 (3.4%) | 2/30 (6.7%) | 0/28 (0%) | 2/35 (5.7%) | ||||
| Other | 5/29 (17.2%) | 1/30 (3.3%) | 1/28 (3.6%) | 4/35 (11.4%) | ||||
| Renal and urinary disorders | ||||||||
| Diuresis | 5/29 (17.2%) | 5/30 (16.7%) | 3/28 (10.7%) | 8/35 (22.9%) | ||||
| Elevated creatinine | 1/29 (3.4%) | 2/30 (6.7%) | 3/28 (10.7%) | 2/35 (5.7%) | ||||
| Elevated potassium | 1/29 (3.4%) | 2/30 (6.7%) | 1/28 (3.6%) | 1/35 (2.9%) | ||||
| Hematuria | 2/29 (6.9%) | 0/30 (0%) | 1/28 (3.6%) | 2/35 (5.7%) | ||||
| Oliguria | 5/29 (17.2%) | 0/30 (0%) | 4/28 (14.3%) | 3/35 (8.6%) | ||||
| Proteinuria | 0/29 (0%) | 0/30 (0%) | 1/28 (3.6%) | 3/35 (8.6%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Apnea | 3/29 (10.3%) | 4/30 (13.3%) | 4/28 (14.3%) | 5/35 (14.3%) | ||||
| Increased fraction of inspired oxygen (FiO2) | 0/29 (0%) | 0/30 (0%) | 2/28 (7.1%) | 1/35 (2.9%) | ||||
| Other | 2/29 (6.9%) | 1/30 (3.3%) | 2/28 (7.1%) | 0/35 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Rash | 1/29 (3.4%) | 0/30 (0%) | 0/28 (0%) | 0/35 (0%) | ||||
| Skin breakdown | 0/29 (0%) | 1/30 (3.3%) | 0/28 (0%) | 0/35 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Investigators must adhere to the Neonatal Research Network Publication policies.
Results Point of Contact
| Name/Title | Dr. Abhik Das |
|---|---|
| Organization | RTI International |
| Phone | 301-770-8214 |
| adas@rti.org |
Responsible Party:
NICHD Neonatal Research Network
ClinicalTrials.gov Identifier:
NCT01030575
Other Study ID Numbers:
- NICHD-NRN-0036-2
- U10HD021364
- U10HD021373
- U10HD021385
- U10HD027851
- U10HD027853
- U10HD027856
- U10HD027871
- U10HD027880
- U10HD027904
- U10HD034216
- U10HD036790
- U10HD040492
- U10HD040689
- U10HD053089
- U10HD053109
- U10HD053119
- U10HD053124
- UL1RR024139
- UL1RR025744
- UL1RR024979
- M01RR008084
First Posted:
Dec 11, 2009
Last Update Posted:
Jun 14, 2022
Last Verified:
Mar 1, 2022