Synergistic Pharmacologic Intervention for Prevention of ROP (SPIPROP Study)

NCT02344225 | Completed Phase 2 Results DMC

• 2 other identifiers: 3496221U54HD071594
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 2, open-label, randomized, multi-center studies in infants and premature infants are necessary to determine treatment and preventative strategies for ROP. This study was designed to: a) target infants at the highest risk of ROP in a large number of centers with variable rates of ROP (all stages and severe ROP or stage 3+); and b) assess whether caffeine plus systemic or ophthalmic NSAID will decrease ROP among infants most at risk for ROP. The study is designed to determine whether the novel treatment regimens are safe and potentially effective for ROP prevention and to obtain requisite data for the development of a Phase III efficacy/safety randomized blinded trial. Since caffeine is used extensively in NICUs as standard of care for ELGANs, no placebo group is included.

Conditions

Retinopathy of Prematurity

Outcome Measures

Primary Outcomes (1)

• Efficacy as Measured by the Number of Participants Presenting With Retinopathy of Prematurity (ROP) and the Rate of Stages/Grade of ROP.

  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.

  50 weeks PCA +/- 7 days

Secondary Outcomes (1)

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability

  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 ROP

Study Arms (3)

Caffeine+Saline IV+Saline drops

ACTIVE COMPARATOR

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

Drug: Caffeine citrate

Caffeine+Ibp IV+Saline drops

EXPERIMENTAL

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

Drug: Ibuprofen

Caffeine+Saline+Ketorolac drops

EXPERIMENTAL

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

Drug: Ketorolac

Interventions

Caffeine citrate DRUG

Caffeine citrate IV (20 mg/kg loading dose, 5 mg/kg/day maintenance dose)

Also known as: Caffeine

Caffeine+Saline IV+Saline drops

Ibuprofen DRUG

Ibuprofen (10 mg/kg loading dose followed by low dose ibuprofen 2.5 mg/kg/day) for 5 days

Also known as: Neoprofen

Caffeine+Ibp IV+Saline drops

Ketorolac DRUG

Ketorolac (Acuvail) eye drops (one drop two times a day) for 14 days

Also known as: Acuvail

Caffeine+Saline+Ketorolac drops

Eligibility Criteria

• Age: Up to 28 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• all infants with a birth weight of less than 1250 grams;
• all infants with a gestational age of 28 weeks or less; and
• all infants who required oxygen therapy and ventilator support within the first 2 days of life.

You may not qualify if:

• major congenital malformations and or chromosomal anomalies including duct-dependent cardiac anomalies;
• maternal antenatal NSAID exposure \<72 hours before birth;
• renal failure or oliguria defined as a urine flow rate \<0.5 mL/kg/hour in the 8 hours prior to randomization. Anuria is acceptable if infant is less than 24 hours of life;
• platelet count \<75,000.mm3;
• clinical bleeding such as oozing from puncture sites; and
• participation in other clinical drug trials while subject participates in this study and for 7 days after last dose of study drug.

Sponsors & Collaborators

• State University of New York - Downstate Medical Center: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Food and Drug Administration (FDA): collaborator

Study Sites (1)

SUNY Downstate Medical Center/University Hospital of Brooklyn

Brooklyn, New York, 11203, United States

Location

MeSH Terms

Conditions

Retinopathy of Prematurity

Interventions

caffeine citrate; Caffeine; Ibuprofen; Ketorolac

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Indomethacin; Indoles

Limitations and Caveats

We did not reach the target number of participants needed to achieve target power and statistically reliable results. Slow enrollment also causes delayed reporting.

Results Point of Contact

• Title: Jacob V. Aranda, MD, PhD, FRCPC, Principal Investigator
• Organization: SUNY Downstate Medical Center

jaranda@downstate.edu

718-270-1912

Study Officials

• Jacob V Aranda, MD, PhD

  SUNY Downstate Medical Center, University Hospital of Brooklyn

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Trials Project Manager

Study Record Dates

• First Submitted: January 7, 2015
• First Posted: January 22, 2015
• Study Start: January 1, 2015
• Primary Completion: June 30, 2018
• Study Completion: June 30, 2018
• Last Updated: May 1, 2020
• Results First Posted: May 1, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)