A Parallel-arm, Single Blind Randomised Controlled Trial Comparing 'AIRWAY PRESSURE RELEASE VENTILATION' and 'LOW-TIDAL VOLUME VENTILATION' in Children With Acute Respiratory Distress Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Twenty-eight-day ventilator-free days
研究概览
简要总结
This study attempts to study a new ventilation mode in children with Acute respiratory distress syndrome (ARDS). Despite decades of research, no intervention has brought about a significant decrease in ARDS mortality. Moreover, most of the studies are adult-based and have been extrapolated to children. Airway pressure release ventilation (APRV) mode is hypothesized to be superior in terms of lower need for sedation, shorter duration of mechanical ventilation, etc. It is unique and the first worldwide randomized controlled trial on APRV mode in children.
We plan to recruit a minimum of 50 children aged (1 month-12 years) in each group. The study is to be conducted at the Post-Graduate Institute of Medical Education and Research (PGIMER), Chandigarh between March 2014 to March 2016. This trial would recruit children with respiratory failure and early ARDS and, randomize them to receive either conventional ventilation or the APRV mode. Rest of the supportive care has also been protocolized so that both groups receive treatment as per the existing best practices in every aspect. The primary outcome being studied is the number of ventilator-free days. The secondary outcomes include length of PICU stay, hospital stay, organ-failure free days, 28 day & 3 month survival, biomarkers of lung injury (IL-6, IL-8, Angiopoeitin-2, soluble-ICAM-1, etc), functional status, Pulmonary function tests, etc. Funding request would be sent to the Indian Council of Medical Research, New Delhi, India.
Assessing lung biomarkers like Interleukin-6 would assess the role of different modes of ventilation in acting as triggers for multi-organ dysfunction as well as for worsening lung injury. This pathbreaking research is likely to open up new avenues upon completion.
详细描述
Study setting:
15-bedded pediatric intensive care unit (PICU) of a multi-specialty, tertiary referral and teaching hospital- the Advanced Pediatrics Centre (APC) in Post-Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India Study period Recruitment: January 2014 to December 2016 Data Analysis: Jan 2017 to June 2017 Study design An open-labelled, parallel-arm, efficacy/feasibility randomized controlled trial Ethics approval Ethics approval has been obtained from the Institute Ethics Committee. The study has been registered with Clinical Trials Registry - India (CTRI) (ctri.nic.in). Informed consent will be obtained from the parents/legal guardian and the conversation would be recorded using a camera (audio-visual documentation of evidence).
Sample size estimation Assuming alpha error of 5% and power of 80% with non-inferiority limit of 4 days (Standard deviation of VFDs being 8.2 days in the conventional low tidal volume ventilation group in pilot trial), sample size was calculated to be 52 per group. As this is a safety and feasibility trial, an interim analysis would be done at 50% enrolment.
Enrolment Parents or legal guardians of children who satisfy the above eligibility criteria will be invited by the investigator to participate in the study. Parents are free not to participate, or to withdraw from the study at any point of time. All children, irrespective of their enrollment in the study, will receive standard pediatric intensive care unit (PICU) care as per the unit's existing protocol. An information sheet (in Hindi/ English) furnishing details of the study will be provided to the parents. Given the fact that all these children are sedated and on mechanical ventilation, obtaining assent would not be feasible in this study.
Randomization Sequence generation A computer-generated, unstratified, block randomization with variable block sizes will be performed to determine group allocation. A person not involved in the study will perform the random number allocation and prepare opaque, sealed envelopes containing the allocation.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 1 Month 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children aged 1 month- 12 years, who are intubated and mechanically ventilated with the following criteria of Acute Respiratory Distress Syndrome:
- •Acute presentation within 1 week of a known clinical insult or new/ worsening respiratory symptoms
- •Bilateral opacities on chest imaging - not fully explained by effusions, lobar/lung collapse, or nodules
- •Respiratory failure is not fully explained by cardiac failure or fluid overload (Echocardiographic assessment to exclude hydrostatic edema)
- •Impaired oxygenation with PaO2/ FiO2 ratio less than 300 or Oxygenation Index greater than 5.3
排除标准
- •Greater than 24 hours since diagnosis of ARDS
- •Co-existing raised intra-cranial pressure/ any other condition necessitating use of high dose of sedation (likely to suppress spontaneous breathing)
- •Radiologically confirmed air leak prior to randomization - Pneumothorax/ Pulmonary interstitial Emphysema
- •Clinical evidence of significant airway obstruction/ severe bronchospasm / reactive airway disease
- •Have received mechanical ventilation for more than 72 hours (before meeting inclusion criteria)
- •Symptomatic or uncorrected congenital heart disease or a right to left intra-cardiac shunt
- •Any underlying condition that is likely to impair spontaneous respiratory drive/ efforts (Eg: Brainstem dysfunction, neuromuscular paralysis)
- •Underlying chronic diseases (Eg: Cystic fibrosis, Chronic lung disease, etc)
研究组 & 干预措施
Airway pressure release ventilation arm
This group of children would be ventilated using the Airway pressure release ventilation (APRV) mode.
Restrictive fluid therapy, protocolized sedo-analgesia titration, steroid therapy, protocolized supportive care, protocolized early enteral nutrition would be provided to both the groups. Biomarkers would be measured in both groups.
干预措施: Airway Pressure Release Ventilation (APRV) (Device)
Airway pressure release ventilation arm
This group of children would be ventilated using the Airway pressure release ventilation (APRV) mode.
Restrictive fluid therapy, protocolized sedo-analgesia titration, steroid therapy, protocolized supportive care, protocolized early enteral nutrition would be provided to both the groups. Biomarkers would be measured in both groups.
干预措施: Methylprednisolone (Drug)
Airway pressure release ventilation arm
This group of children would be ventilated using the Airway pressure release ventilation (APRV) mode.
Restrictive fluid therapy, protocolized sedo-analgesia titration, steroid therapy, protocolized supportive care, protocolized early enteral nutrition would be provided to both the groups. Biomarkers would be measured in both groups.
干预措施: Restrictive fluid therapy (Other)
Airway pressure release ventilation arm
This group of children would be ventilated using the Airway pressure release ventilation (APRV) mode.
Restrictive fluid therapy, protocolized sedo-analgesia titration, steroid therapy, protocolized supportive care, protocolized early enteral nutrition would be provided to both the groups. Biomarkers would be measured in both groups.
干预措施: sedo-analgesia titration (Drug)
Airway pressure release ventilation arm
This group of children would be ventilated using the Airway pressure release ventilation (APRV) mode.
Restrictive fluid therapy, protocolized sedo-analgesia titration, steroid therapy, protocolized supportive care, protocolized early enteral nutrition would be provided to both the groups. Biomarkers would be measured in both groups.
干预措施: Protocolized early enteral nutrition (Other)
Airway pressure release ventilation arm
This group of children would be ventilated using the Airway pressure release ventilation (APRV) mode.
Restrictive fluid therapy, protocolized sedo-analgesia titration, steroid therapy, protocolized supportive care, protocolized early enteral nutrition would be provided to both the groups. Biomarkers would be measured in both groups.
干预措施: Protocolized supportive care (Other)
Airway pressure release ventilation arm
This group of children would be ventilated using the Airway pressure release ventilation (APRV) mode.
Restrictive fluid therapy, protocolized sedo-analgesia titration, steroid therapy, protocolized supportive care, protocolized early enteral nutrition would be provided to both the groups. Biomarkers would be measured in both groups.
干预措施: Biomarker Assay (Other)
Low-tidal volume ventilation arm
Low-tidal volume ventilation using pressure-regulated volume control mode with target tidal volume of 6 ml/kg or less and other lung-protective strategies. Restrictive fluid therapy, protocolized sedo-analgesia titration, steroid therapy, protocolized supportive care, protocolized early enteral nutrition would be provided to both the groups. Biomarkers would be measured in both groups
干预措施: Low-tidal volume ventilation (Other)
Low-tidal volume ventilation arm
Low-tidal volume ventilation using pressure-regulated volume control mode with target tidal volume of 6 ml/kg or less and other lung-protective strategies. Restrictive fluid therapy, protocolized sedo-analgesia titration, steroid therapy, protocolized supportive care, protocolized early enteral nutrition would be provided to both the groups. Biomarkers would be measured in both groups
干预措施: Methylprednisolone (Drug)
Low-tidal volume ventilation arm
Low-tidal volume ventilation using pressure-regulated volume control mode with target tidal volume of 6 ml/kg or less and other lung-protective strategies. Restrictive fluid therapy, protocolized sedo-analgesia titration, steroid therapy, protocolized supportive care, protocolized early enteral nutrition would be provided to both the groups. Biomarkers would be measured in both groups
干预措施: Restrictive fluid therapy (Other)
Low-tidal volume ventilation arm
Low-tidal volume ventilation using pressure-regulated volume control mode with target tidal volume of 6 ml/kg or less and other lung-protective strategies. Restrictive fluid therapy, protocolized sedo-analgesia titration, steroid therapy, protocolized supportive care, protocolized early enteral nutrition would be provided to both the groups. Biomarkers would be measured in both groups
干预措施: sedo-analgesia titration (Drug)
Low-tidal volume ventilation arm
Low-tidal volume ventilation using pressure-regulated volume control mode with target tidal volume of 6 ml/kg or less and other lung-protective strategies. Restrictive fluid therapy, protocolized sedo-analgesia titration, steroid therapy, protocolized supportive care, protocolized early enteral nutrition would be provided to both the groups. Biomarkers would be measured in both groups
干预措施: Protocolized early enteral nutrition (Other)
Low-tidal volume ventilation arm
Low-tidal volume ventilation using pressure-regulated volume control mode with target tidal volume of 6 ml/kg or less and other lung-protective strategies. Restrictive fluid therapy, protocolized sedo-analgesia titration, steroid therapy, protocolized supportive care, protocolized early enteral nutrition would be provided to both the groups. Biomarkers would be measured in both groups
干预措施: Protocolized supportive care (Other)
Low-tidal volume ventilation arm
Low-tidal volume ventilation using pressure-regulated volume control mode with target tidal volume of 6 ml/kg or less and other lung-protective strategies. Restrictive fluid therapy, protocolized sedo-analgesia titration, steroid therapy, protocolized supportive care, protocolized early enteral nutrition would be provided to both the groups. Biomarkers would be measured in both groups
干预措施: Biomarker Assay (Other)
结局指标
主要结局
Twenty-eight-day ventilator-free days
时间窗: 28 days
次要结局
- All-cause mortality(Three months)
- Interleukin-6 levels(72 hours of enrolment)
- Arterial lactate levels(72 hours)
- Cumulative dose of sedation(7 days)
- Cumulative dose of analgesic(7 days)
- Cumulative dose of neuromuscular blocking agent(7 days)
- Organ-failure-free-days(28 days)
- Twenty-eight-day survival(28 days)
- Length of PICU stay(Up to 3 months)
- Time-to-recovery of lung injury(Up to 28 days)
- Pediatric Cerebral performance category(6 Months)
- Pediatric Overall performance category(6 months)
- Number of children with adverse events(3 years)
- Spirometry(6 months)
- Pediatric overall performance category(3 months)
- Pediatric cerebral performance category(3 months)
- Percentage reduction in 'oxygenation Index'(6 hours)
- Radiological score(48 hours)
- Duration of inotropic requirement(up to 7 days)
- Vaso-active inotropic score(72 hours)
- Requirement for renal replacement therapy(28 days)
- Pediatric Logistic Organ Dysfunction (PELOD) score(7 days)
研究者
Dr. Saptharishi L G, MBBS, MD
DM (Pediatric Critical Care) Senior Resident, Division of Pediatric Critical care, Dept. of Pediatrics
Post Graduate Institute of Medical Education and Research, Chandigarh