Synergistic Pharmacologic Intervention for Prevention of ROP (SPIPROP STUDY)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Efficacy as Measured by the Number of Participants Presenting With Retinopathy of Prematurity (ROP) and the Rate of Stages/Grade of ROP.
研究概览
简要总结
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.
详细描述
This study will evaluate the safety, tolerability and PK-PD of, and to compare and contrast, IV Ibuprofen with Caffeine and Ketorolac eye drops with Caffeine in ELGAN infants <28 weeks GA for 14 days duration to treat and preferably prevent ROP associated with prematurity and ELGAN. The specific aims of this trial are:
Aim 1: To establish the synergistic effect of local ophthalmic NSIADs and systemic caffeine as optimal therapies for the attenuation and/or prevention of severe ROP. Hypothesis: Ocular Ketorolac or systemic Ibuprofen potentiated with systemic Caffeine will prevent or diminish the severity of ROP. We will: a) Evaluate the safety, tolerability, and efficacy of early postnatal local ophthalmic NSIADs for prevention of severe ROP in ELGANs. b) Determine the pharmacokinetics, pharmacodymanics and pharmacogenomics of NSAIDs potentiated with caffeine for prevention of ROP.
Aim 2: To identify a "critical" number of arterial oxygen desaturations as a key risk factor for severe ROP.
Hypothesis: A "critical" number of daily arterial oxygen desaturations during the first two weeks of life is a key risk factor for severe ROP. We will: a) Further define the role of VEGF, IGF, MMPs, and ROS in ROP and correlate the levels with the number of arterial oxygen desaturations. b) Establish and identify whether increased serum VEGF in infants with severe ROP is the diffusible isoform VEGF121. This isoform is formed from VEGF proteolysis by plasmin and MMPs. MMPs also cleave Notch/Dll4, which acts as a regulator of VEGF signaling.
Aim 3: To determine whether infants at risk for severe ROP are haploinsufficient for the delta-like ligand 4 (Dll4).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- — 至 28 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Neonates at high risk for ROP as outlined by the American Academy of Pediatrics, Section on Ophthalmology; American Association for Pediatric Ophthalmology and Strabismus; and American Academy of Ophthalmology (129) will be enrolled. Inclusion criteria are:
- •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.
排除标准
- •Exclusion criteria are:
- •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.
研究组 & 干预措施
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
干预措施: Caffeine citrate (Drug)
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
干预措施: Ibuprofen (Drug)
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
干预措施: Ketorolac (Drug)
结局指标
主要结局
Efficacy as Measured by the Number of Participants Presenting With Retinopathy of Prematurity (ROP) and the Rate of Stages/Grade of ROP.
时间窗: 50 weeks PCA +/- 7 days
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.
次要结局
- 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)
研究者
Khadija Sikriti
Clinical Trials Project Manager
State University of New York - Downstate Medical Center