A Phase 2 Randomized Double-blind, Placebo-controlled Clinical Trial of Intravenous Citrulline for Vaso-occlusive Pain Episode in Hospitalized Patients With Sickle Cell Disease (CONQUER SCD Pain Trial)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 99
- 试验地点
- 1
- 主要终点
- Time-to-crisis resolution
研究概览
简要总结
The goal of this clinical trial is to learn if intravenous citrulline works to treat acute pain in hospitalized patients with sickle cell disease. It will also learn about the safety of intravenous citrulline. The main questions it aims to answer are:
- Does intravenous citrulline decrease the duration of sickle cell pain during hospitalization
- What medical problems do participants have when taking intravenous citrulline? Researchers will compare intravenous citrulline to a placebo (a look-alike substance that contains no drug) to see if intravenous citrulline works to treat acute pain.
Participants will:
- Receive baseline tests and intravenous citrulline for 16 hours during the hospital stay
- After hospital discharge, visit the clinic in about 30 days for checkup and tests
详细描述
This is a single-center phase 2 randomized double-blind, placebo-controlled trial of intravenous L-citrulline for sickle cell patients ages 4 to 21 years experiencing a vaso-occlusive pain crisis episode (VOE). Eligible subjects will have a documented history of sickle cell disease and inpatient hospitalization for treatment of acute pain with parenteral opioid. Subjects will be randomized to receive high dose intravenous L-citrulline, low dose intravenous L-citrulline or placebo in addition to standard of care. Subjects will be followed closely to evaluate time-to-crisis resolution as the primary outcome defined by time from first dose of intravenous study drug/placebo to the last dose of parenteral opioid prior to hospital discharge. Participants will be monitored for any adverse events including 30-day re-hospitalization rates. Total opioid consumption during the time-to-crisis resolution will be compared between the three arms. In addition, exploratory outcomes will be evaluated for pain score, tissue blood flow, genetic and candidate biomarkers related to vaso-occlusion.
Objectives Primary Objective
• To demonstrate the efficacy of intravenous L-citrulline in reducing the time-to-crisis resolution in sickle cell subjects experiencing a vaso-occlusive pain crisis episode (VOE).
Secondary Objectives
- To evaluate the safety of intravenous L-citrulline in the treatment of VOE
- To determine if intravenous L-citrulline improves cumulative opioid consumption during the treatment of VOE Exploratory Objectives
- To determine if intravenous L-citrulline improves pain scores during the hospitalization
- To determine if intravenous L-citrulline improves 30-day re-hospitalization rates
- To determine the pharmacokinetic (PK) profile of intravenous L-citrulline
- To evaluate whether intravenous L-citrulline improves tissue blood flow and candidate biomarkers related to vaso-occlusion.
- To assess whether genetic single nucleotide polymorphisms related to the nitric oxide pathway influence study outcomes
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 4 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Sickle cell disease (all genotypes)
- •Patients with sickle cell disease ages 4 to 21 years old
- •Presence of sickle cell vaso-occlusive pain episode requiring hospitalization and parenteral opioid therapy
- •Able to randomize to study drug/placebo within 12 hours of first dose of parenteral opioid in the Emergency Department
排除标准
- •Current pain lasting >3 days.
- •>9 hospitalizations in the prior year
- •Presence of any other complication related to sickle cell disease requiring the hospitalization such as splenic sequestration, hepatic sequestration, stroke, transient ischemic attack, etc.
- •History of opioid use disorder, chronic pain or medical regimen requiring daily opioid use.
- •Severe anemia (hemoglobin <6g/dL)
- •Pregnant (as confirmed by a positive urine pregnancy test) or lactating female.
- •Alanine/aspartate transferase >2x upper limit of normal laboratory range for age.
- •Subject has the following serum creatinine:
- •Age 4 to 13 years > 0.9 mg/dL
- •Age 14 to 17 years 1.0 mg/dL
- •Age ≥18 years >1.5mg/dL
- •Presence of acute chest syndrome, sepsis, bacterial infection, hemodynamic instability
- •Use of L-glutamine
- •History of allergic reaction to L-citrulline products
研究组 & 干预措施
Placebo
干预措施: Placebo (Other)
Low dose intravenous L-citrulline
干预措施: L-citrulline (Drug)
High dose intravenous L-citrulline
干预措施: L-citrulline (Drug)
结局指标
主要结局
Time-to-crisis resolution
时间窗: Baseline to 30 days
Change in time-to-crisis resolution as defined by the time (in hours) from first dose of intravenous study drug or placebo to the time of last dose of intravenous opioid during hospitalization
次要结局
- Safety(Baseline to 30 days)
- Opioid consumption(Baseline to 30 days)
- Pain scores(Baseline to 30 days)
研究者
Suvankar Majumdar
Chief of Hematology
Children's National Research Institute