Trial Outcomes & Findings for Synergistic Pharmacologic Intervention for Prevention of ROP (SPIPROP Study) (NCT NCT02344225)
NCT ID: NCT02344225
Last Updated: 2020-05-01
Results Overview
ROP (all grades) will be graded using International ROP Classification and severe ROP (Stage 3+ disease) or need for laser or Avastin The rate of mild (stage 1), moderate (stage 2) and severe ROP (stages \>3) will be calculated as the number of infants diagnosed with ROP over the number of infants receiving retinal examinations. The study enrolled only 14 of the projected sample of 120, and the low enrollment did not allow meaningful analyses of efficacy and safety.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
14 participants
Primary outcome timeframe
50 weeks PCA +/- 7 days
Results posted on
2020-05-01
Participant Flow
The study started on Jan 01, 2015, and ended on Jun 30, 2018. Ninety-Eight (98) participants have been screened at five study sites. However, only 14 participants were enrolled. The reasons for poor enrollment were mostly due to refusal to participate, and some did not meet the eligibility criteria. All participants completed the study.
The study screened 98 subjects when most mothers were admitted for preterm labor. They were treated successfully with tocolysis and other clinical managements (e.g. bed rest, magnesium sulfate etc.) which resulted in prolonging the pregnancy beyond 28 weeks at which time they met exclusion criteria and no longer eligible for the study..
Participant milestones
| Measure |
Caffeine+Saline IV+Saline Drops
Caffeine citrate IV (20 mg/kg loading dose, 5 mg/kg/day maintenance dose) plus placebo saline IV (1 ml/kg followed by 0.25 ml/kg) for 5 days plus sterile normal saline (one drop two times a day) for 14 days (n=40); Caffeine is the intervention
Caffeine citrate: Caffeine citrate IV (20 mg/kg loading dose, 5 mg/kg/day maintenance dose)
|
Caffeine+Ibp IV+Saline Drops
Caffeine citrate as described in group 1, plus Ibuprofen (10 mg/kg loading dose followed by low dose ibuprofen 2.5 mg/kg/day) for 5 days plus sterile normal saline (one drop two times a day) for 14 days (n=40); Ibuprofen is the intervention
Ibuprofen: Ibuprofen (10 mg/kg loading dose followed by low dose ibuprofen 2.5 mg/kg/day) for 5 days
|
Caffeine+Saline+Ketorolac Drops
Caffeine citrate plus saline IV placebo as described in group 1, and Ketorolac (Acuvail) eye drops (one drop two times a day) for 14 days (n=40); Ketorolac is the intervention
Ketorolac: Ketorolac (Acuvail) eye drops (one drop two times a day) for 14 days
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
3
|
5
|
|
Overall Study
COMPLETED
|
6
|
3
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Synergistic Pharmacologic Intervention for Prevention of ROP (SPIPROP Study)
Baseline characteristics by cohort
| Measure |
Caffeine+Saline IV+Saline Drops
n=6 Participants
Caffeine citrate IV (20 mg/kg loading dose, 5 mg/kg/day maintenance dose) plus placebo saline IV (1 ml/kg followed by 0.25 ml/kg) for 5 days plus sterile normal saline (one drop two times a day) for 14 days (n=40); Caffeine is the intervention
Caffeine citrate: Caffeine citrate IV (20 mg/kg loading dose, 5 mg/kg/day maintenance dose)
|
Caffeine+Ibp IV+Saline Drops
n=3 Participants
Caffeine citrate as described in group 1, plus Ibuprofen (10 mg/kg loading dose followed by low dose ibuprofen 2.5 mg/kg/day) for 5 days plus sterile normal saline (one drop two times a day) for 14 days (n=40); Ibuprofen is the intervention
Ibuprofen: Ibuprofen (10 mg/kg loading dose followed by low dose ibuprofen 2.5 mg/kg/day) for 5 days
|
Caffeine+Saline+Ketorolac Drops
n=5 Participants
Caffeine citrate plus saline IV placebo as described in group 1, and Ketorolac (Acuvail) eye drops (one drop two times a day) for 14 days (n=40); Ketorolac is the intervention
Ketorolac: Ketorolac (Acuvail) eye drops (one drop two times a day) for 14 days
|
Total
n=14 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
25.5 Gestational Age in Week
n=93 Participants
|
26.7 Gestational Age in Week
n=4 Participants
|
26.6 Gestational Age in Week
n=27 Participants
|
26.6 Gestational Age in Week
n=483 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
7 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
7 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
8 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
8 Participants
n=483 Participants
|
|
Birth Weight (grams)
|
731.7 Grams
n=93 Participants
|
1119.3 Grams
n=4 Participants
|
1020 Grams
n=27 Participants
|
917.7 Grams
n=483 Participants
|
PRIMARY outcome
Timeframe: 50 weeks PCA +/- 7 daysROP (all grades) will be graded using International ROP Classification and severe ROP (Stage 3+ disease) or need for laser or Avastin The rate of mild (stage 1), moderate (stage 2) and severe ROP (stages \>3) will be calculated as the number of infants diagnosed with ROP over the number of infants receiving retinal examinations. The study enrolled only 14 of the projected sample of 120, and the low enrollment did not allow meaningful analyses of efficacy and safety.
Outcome measures
| Measure |
Caffeine+Saline IV+Saline Drops
n=6 Participants
Caffeine citrate IV (20 mg/kg loading dose, 5 mg/kg/day maintenance dose) plus placebo saline IV (1 ml/kg followed by 0.25 ml/kg) for 5 days plus sterile normal saline (one drop two times a day) for 14 days (n=40); Caffeine is the intervention
Caffeine citrate: Caffeine citrate IV (20 mg/kg loading dose, 5 mg/kg/day maintenance dose)
|
Caffeine+Ibp IV+Saline Drops
n=3 Participants
Caffeine citrate as described in group 1, plus Ibuprofen (10 mg/kg loading dose followed by low dose ibuprofen 2.5 mg/kg/day) for 5 days plus sterile normal saline (one drop two times a day) for 14 days (n=40); Ibuprofen is the intervention
Ibuprofen: Ibuprofen (10 mg/kg loading dose followed by low dose ibuprofen 2.5 mg/kg/day) for 5 days
|
Caffeine+Saline+Ketorolac Drops
n=5 Participants
Caffeine citrate plus saline IV placebo as described in group 1, and Ketorolac (Acuvail) eye drops (one drop two times a day) for 14 days (n=40); Ketorolac is the intervention
Ketorolac: Ketorolac (Acuvail) eye drops (one drop two times a day) for 14 days
|
|---|---|---|---|
|
Efficacy as Measured by the Number of Participants Presenting With Retinopathy of Prematurity (ROP) and the Rate of Stages/Grade of ROP.
No ROP
|
5 Participants
|
3 Participants
|
4 Participants
|
|
Efficacy as Measured by the Number of Participants Presenting With Retinopathy of Prematurity (ROP) and the Rate of Stages/Grade of ROP.
Mild ROP (Stage 1)
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Efficacy as Measured by the Number of Participants Presenting With Retinopathy of Prematurity (ROP) and the Rate of Stages/Grade of ROP.
Moderate ROP (Stage2)
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Efficacy as Measured by the Number of Participants Presenting With Retinopathy of Prematurity (ROP) and the Rate of Stages/Grade of ROP.
severe ROP (stages >3)
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Eye examinations was done at standard of care through discharge and once, at 50 weeks PCA. All infants underwent routine eye examination by a pediatric ophthalmologist according to the International Classification for ROPWe did not reach the target number of participants needed to measure statistically reliable outcome measure. The secondary outcome measure included Intraventricular hemorrhage (Papile's criteria) and ocular examination for corneal lesions.
Outcome measures
| Measure |
Caffeine+Saline IV+Saline Drops
n=6 Participants
Caffeine citrate IV (20 mg/kg loading dose, 5 mg/kg/day maintenance dose) plus placebo saline IV (1 ml/kg followed by 0.25 ml/kg) for 5 days plus sterile normal saline (one drop two times a day) for 14 days (n=40); Caffeine is the intervention
Caffeine citrate: Caffeine citrate IV (20 mg/kg loading dose, 5 mg/kg/day maintenance dose)
|
Caffeine+Ibp IV+Saline Drops
n=3 Participants
Caffeine citrate as described in group 1, plus Ibuprofen (10 mg/kg loading dose followed by low dose ibuprofen 2.5 mg/kg/day) for 5 days plus sterile normal saline (one drop two times a day) for 14 days (n=40); Ibuprofen is the intervention
Ibuprofen: Ibuprofen (10 mg/kg loading dose followed by low dose ibuprofen 2.5 mg/kg/day) for 5 days
|
Caffeine+Saline+Ketorolac Drops
n=5 Participants
Caffeine citrate plus saline IV placebo as described in group 1, and Ketorolac (Acuvail) eye drops (one drop two times a day) for 14 days (n=40); Ketorolac is the intervention
Ketorolac: Ketorolac (Acuvail) eye drops (one drop two times a day) for 14 days
|
|---|---|---|---|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
|
0 Participants
|
0 Participants
|
1 Participants
|
POST_HOC outcome
Timeframe: on average 6 monthsSafety as measured by Length of hospital stay
Outcome measures
| Measure |
Caffeine+Saline IV+Saline Drops
n=6 Participants
Caffeine citrate IV (20 mg/kg loading dose, 5 mg/kg/day maintenance dose) plus placebo saline IV (1 ml/kg followed by 0.25 ml/kg) for 5 days plus sterile normal saline (one drop two times a day) for 14 days (n=40); Caffeine is the intervention
Caffeine citrate: Caffeine citrate IV (20 mg/kg loading dose, 5 mg/kg/day maintenance dose)
|
Caffeine+Ibp IV+Saline Drops
n=3 Participants
Caffeine citrate as described in group 1, plus Ibuprofen (10 mg/kg loading dose followed by low dose ibuprofen 2.5 mg/kg/day) for 5 days plus sterile normal saline (one drop two times a day) for 14 days (n=40); Ibuprofen is the intervention
Ibuprofen: Ibuprofen (10 mg/kg loading dose followed by low dose ibuprofen 2.5 mg/kg/day) for 5 days
|
Caffeine+Saline+Ketorolac Drops
n=5 Participants
Caffeine citrate plus saline IV placebo as described in group 1, and Ketorolac (Acuvail) eye drops (one drop two times a day) for 14 days (n=40); Ketorolac is the intervention
Ketorolac: Ketorolac (Acuvail) eye drops (one drop two times a day) for 14 days
|
|---|---|---|---|
|
Length of Hospital Stay
|
126 Days
Standard Deviation 30.1
|
74 Days
Standard Deviation 9.0
|
68 Days
Standard Deviation 21.8
|
Adverse Events
Caffeine+Saline IV+Saline Drops
Serious events: 6 serious events
Other events: 6 other events
Deaths: 0 deaths
Caffeine+Ibp IV+Saline Drops
Serious events: 3 serious events
Other events: 3 other events
Deaths: 0 deaths
Caffeine+Saline+Ketorolac Drops
Serious events: 2 serious events
Other events: 5 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Caffeine+Saline IV+Saline Drops
n=6 participants at risk
Caffeine citrate IV (20 mg/kg loading dose, 5 mg/kg/day maintenance dose) plus placebo saline IV (1 ml/kg followed by 0.25 ml/kg) for 5 days plus sterile normal saline (one drop two times a day) for 14 days (n=40); Caffeine is the intervention
Caffeine citrate: Caffeine citrate IV (20 mg/kg loading dose, 5 mg/kg/day maintenance dose)
|
Caffeine+Ibp IV+Saline Drops
n=3 participants at risk
Caffeine citrate as described in group 1, plus Ibuprofen (10 mg/kg loading dose followed by low dose ibuprofen 2.5 mg/kg/day) for 5 days plus sterile normal saline (one drop two times a day) for 14 days (n=40); Ibuprofen is the intervention
Ibuprofen: Ibuprofen (10 mg/kg loading dose followed by low dose ibuprofen 2.5 mg/kg/day) for 5 days
|
Caffeine+Saline+Ketorolac Drops
n=5 participants at risk
Caffeine citrate plus saline IV placebo as described in group 1, and Ketorolac (Acuvail) eye drops (one drop two times a day) for 14 days (n=40); Ketorolac is the intervention
Ketorolac: Ketorolac (Acuvail) eye drops (one drop two times a day) for 14 days
|
|---|---|---|---|
|
Gastrointestinal disorders
Death
|
0.00%
0/6 • The adverse events data were collected over an average of 6 months.
|
0.00%
0/3 • The adverse events data were collected over an average of 6 months.
|
40.0%
2/5 • Number of events 2 • The adverse events data were collected over an average of 6 months.
|
|
Respiratory, thoracic and mediastinal disorders
Apnea
|
100.0%
6/6 • The adverse events data were collected over an average of 6 months.
|
100.0%
3/3 • The adverse events data were collected over an average of 6 months.
|
40.0%
2/5 • The adverse events data were collected over an average of 6 months.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary dysplasia (BPD
|
16.7%
1/6 • The adverse events data were collected over an average of 6 months.
|
0.00%
0/3 • The adverse events data were collected over an average of 6 months.
|
40.0%
2/5 • The adverse events data were collected over an average of 6 months.
|
|
Gastrointestinal disorders
Necrotizing enterocolitis (NEC)
|
0.00%
0/6 • The adverse events data were collected over an average of 6 months.
|
0.00%
0/3 • The adverse events data were collected over an average of 6 months.
|
40.0%
2/5 • The adverse events data were collected over an average of 6 months.
|
|
Nervous system disorders
Intraventricular hemorrhage (IVH)
|
0.00%
0/6 • The adverse events data were collected over an average of 6 months.
|
0.00%
0/3 • The adverse events data were collected over an average of 6 months.
|
20.0%
1/5 • The adverse events data were collected over an average of 6 months.
|
|
Congenital, familial and genetic disorders
Patent ductus arteriosus (PDA)
|
33.3%
2/6 • The adverse events data were collected over an average of 6 months.
|
33.3%
1/3 • The adverse events data were collected over an average of 6 months.
|
0.00%
0/5 • The adverse events data were collected over an average of 6 months.
|
Other adverse events
| Measure |
Caffeine+Saline IV+Saline Drops
n=6 participants at risk
Caffeine citrate IV (20 mg/kg loading dose, 5 mg/kg/day maintenance dose) plus placebo saline IV (1 ml/kg followed by 0.25 ml/kg) for 5 days plus sterile normal saline (one drop two times a day) for 14 days (n=40); Caffeine is the intervention
Caffeine citrate: Caffeine citrate IV (20 mg/kg loading dose, 5 mg/kg/day maintenance dose)
|
Caffeine+Ibp IV+Saline Drops
n=3 participants at risk
Caffeine citrate as described in group 1, plus Ibuprofen (10 mg/kg loading dose followed by low dose ibuprofen 2.5 mg/kg/day) for 5 days plus sterile normal saline (one drop two times a day) for 14 days (n=40); Ibuprofen is the intervention
Ibuprofen: Ibuprofen (10 mg/kg loading dose followed by low dose ibuprofen 2.5 mg/kg/day) for 5 days
|
Caffeine+Saline+Ketorolac Drops
n=5 participants at risk
Caffeine citrate plus saline IV placebo as described in group 1, and Ketorolac (Acuvail) eye drops (one drop two times a day) for 14 days (n=40); Ketorolac is the intervention
Ketorolac: Ketorolac (Acuvail) eye drops (one drop two times a day) for 14 days
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Distress Syndrome (RDS)
|
100.0%
6/6 • The adverse events data were collected over an average of 6 months.
|
100.0%
3/3 • The adverse events data were collected over an average of 6 months.
|
100.0%
5/5 • The adverse events data were collected over an average of 6 months.
|
Additional Information
Jacob V. Aranda, MD, PhD, FRCPC, Principal Investigator
SUNY Downstate Medical Center
Phone: 718-270-1912
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place