Inhaled Mometasone to Promote Reduction in Vasoocclusive Events 2
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Soluble Vascular Cell Adhesion Molecule (sVCAM) level
研究概览
简要总结
The study team proposes a triple-blind, placebo-controlled, phase II clinical trial of once-daily inhaled mometasone for 48 weeks (with 4-week washout at study completion) in individuals with Sickle Cell Disease (SCD) who report episodic cough or wheeze (ECW) but do not have asthma. Patients will be recruited from and followed in SCD clinics at participating sites. The primary endpoint will be a reduction in sVCAM level of 20% or more in comparison to placebo.
详细描述
Dose rationale: Mometasone furoate 220mcg dry powder inhalation is a low-moderate ICS dose that can be given once daily. Higher doses can have systemic effects and systemic glucocorticoids can precipitate rebound SCD pain when discontinued.
Adaptive, covariate-balanced randomization: While the sample size of the study will be fixed at 80 participants, instead of standard blocked or stratified randomization, the study team will use adaptive covariate-balanced randomization to minimize imbalance of important covariates. This will reduce the need to use multivariable techniques (which perform poorly in small samples) to adjust post hoc for differences between treatment groups. Covariates will include age, use of hydroxyurea, previous rate of Emergency Department (ED) utilization for SCD pain, and recruitment site.
Follow up Schedule: There will be in-person visits every 8 weeks. In addition, a blinded research coordinator will contact participants by phone at 2-weeks and 4-weeks after enrollment and 4-weeks after each in-person follow up to encourage protocol adherence and collect data about adverse events and healthcare utilization.
Post-protocol observation period: The study will be complete at 48 weeks. A final follow up visit will occur at 52 weeks (4-weeks after study protocol completed) to collect pain diary and adverse event data and to identify the proportion of the ICS group who want to continue ICS. In the event that individuals wish to continue ICS, the PI will contact the participant's treating physician to discuss.
Data elements: A wide range of clinical and translational data will be collected during the study. Baseline data will include demographic and clinical variables regarding SCD severity, previous complications and respiratory surveys. Blood will be collected for standard-of-care labs and analysis of serum inflammatory cytokines. Pulmonary function testing including spirometry and Exhaled Nitric Oxide (eNO) will be performed. Health related quality of life will be collected via ASCQ-Me survey. Patients will also be followed with follow-up phone calls and prospective chart review for one year to identify hospital visits and other SCD complications.
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)
盲法说明
Quadruple blind
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants age 18 and older with severe SCD phenotypes (Hb SS and Sβthalassemia0):
- •Do not have asthma (see exclusion criteria)
- •Not currently having a painful crisis (as defined by validated pain diary questions)
- •Do not have acute respiratory symptoms
- •Report of recent ECW (answers "Yes" to any question in Box 1)
- •Participant is already medically optimized (i.e. already on maximum dose hydroxyurea unless contraindicated and not undergoing medication titration).
排除标准
- •Participant screens positive for possible undiagnosed asthma (Box 2)
- •Pregnant or planning to become pregnant
- •> 15 ED visits for SCD pain over the previous 12 months (due to concern for multi-factorial pain that may be less responsive to SCD therapies)
- •Have been discharged from the hospital within the previous 7 days.
研究组 & 干预措施
Placebo
Once daily inhaled placebo
干预措施: Placebo (Drug)
Mometasone
Inhaled Mometasone Furoate 220 mcg DPI
干预措施: Mometasone (Drug)
结局指标
主要结局
Soluble Vascular Cell Adhesion Molecule (sVCAM) level
时间窗: Baseline and one year
Change in sVCAM level at one year compared to baseline. sVCAM is a biomarker used as a surrogate for red blood cell (RBC) adhesivity and overall disease severity in SCD.
次要结局
- Hemoglobin level(Baseline and one year)
- Bilirubin (Direct and Indirect) level(Baseline and one year)
- Plasma Free Hemoglobin level(Baseline and one year)
- LDH level(Baseline and one year)
- Leukocyte Count level(Baseline and one year)
- Brain Natriuretic Peptide(Baseline and one year)
- Spirometry(Baseline and one year)
- Number of Pneumonia Episodes(One year)
- Number of ICU Admissions(One year)
- O-Link Inflammation Panel Sputum(Baseline and one year)
- Medication Adherence Self-Report Scale for Asthma (MARS-A)(At one year)
- Number of Deaths(One year)
- O-Link Inflammation Panel Serum(Baseline and one year)
- Sputum Immune Cell Subpopulations CyTOF(Baseline and one year)
- Pain Score(Up to one year)
- Number Hospitalizations for SCD Pain(One year)
- Number of Observation Unit Admission for SCD Pain(One year)
- Number of Overnight Stays for SCD Pain(One year)
- Number of Outpatient Infusion Visits for SCD Pain(One year)
- Multiplex Cytokine Panel Serum(Baseline and one year)
- Whole Blood Frequency of Aged Neutrophils CyTOF(Baseline and one year)
- Reticulocyte Count level(Baseline and one year)
- Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) survey(Baseline and one year)
- Sputum Frequency of Aged Neutrophils CyTOF(Baseline and one year)
- Sputum frequency of activated monocytes CyTOF(Baseline and one year)
- Platelet Count level(Baseline and one year)
- Exhaled Nitric Oxide(Baseline and one year)
- Number of ED Visits for SCD Pain(One year)
- Whole Blood Immune Cell Subpopulations CyTOF(Baseline and one year)
- 6-Minute Walk Test(Baseline and one year)
研究者
Jeffrey Glassberg
Associate Professor
Icahn School of Medicine at Mount Sinai