Trial of an Alternate Mode of Providing Artificial Breaths to Children With Very Severe Pneumonia

NCT02167698 | Terminated DMC

• 1 other identifier: CTRI/2014/06/004677
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Respiratory Distress Syndrome (ARDS)

Keywords

Pediatric acute respiratory distress syndrome; Mechanical ventilation; Airway pressure release ventilation; Conventional low-tidal volume ventilation

Outcome Measures

Primary Outcomes (1)

• Twenty-eight-day ventilator-free days

  28 days

Secondary Outcomes (23)

• Twenty-eight-day survival

  28 days

• Length of PICU stay

  Up to 3 months

• Organ-failure-free-days

  28 days

• Time-to-recovery of lung injury

  Up to 28 days

• Number of children with adverse events

  3 years

Other Outcomes (5)

• Recruitment rate

  3 years

• Rate of enrolment among eligible children

  3 years

• Contamination rate

  3 years

Study Arms (2)

Airway pressure release ventilation arm

EXPERIMENTAL

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.

Device: Airway Pressure Release Ventilation (APRV); Drug: Methylprednisolone; Other: Restrictive fluid therapy; Drug: sedo-analgesia titration; Other: Protocolized early enteral nutrition; Other: Protocolized supportive care; Other: Biomarker Assay

Low-tidal volume ventilation arm

ACTIVE COMPARATOR

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

Other: Low-tidal volume ventilation; Drug: Methylprednisolone; Other: Restrictive fluid therapy; Drug: sedo-analgesia titration; Other: Protocolized early enteral nutrition; Other: Protocolized supportive care; Other: Biomarker Assay

Interventions

Airway Pressure Release Ventilation (APRV) DEVICE

This is a newer mode of ventilation that has been hypothesized to be equivalent or even superior to the conventional low-tidal volume mode of ventilation

Also known as: BiLevel, BiPAP

Airway pressure release ventilation arm

Low-tidal volume ventilation OTHER

This mode of ventilation is the standard of care worldwide for ventilating children with ARDS.

Also known as: Lung-protective ventilation

Low-tidal volume ventilation arm

Methylprednisolone DRUG

Children with primary ARDS presenting within the first 14 days would receive IV low dose Methylprednisolone infusion.

Airway pressure release ventilation arm; Low-tidal volume ventilation arm

Restrictive fluid therapy OTHER

Fluid \& hemodynamics would be titrated as per pre-designed decision-making protocols

Airway pressure release ventilation arm; Low-tidal volume ventilation arm

sedo-analgesia titration DRUG

Airway pressure release ventilation arm; Low-tidal volume ventilation arm

Protocolized early enteral nutrition OTHER

Early enteral nutrition and attempt to meet calorie-protein goals

Airway pressure release ventilation arm; Low-tidal volume ventilation arm

Protocolized supportive care OTHER

Eye care, chlorhexidine mouth wash Q6 hourly, Strict aseptic precautions prior to any procedures, Skin care \& bed sore prevention, Adequate pulmonary toileting and chest physiotherapy, frequent position changes, limb physiotherapy, family-centered care

Airway pressure release ventilation arm; Low-tidal volume ventilation arm

Biomarker Assay OTHER

Biomarker Assay for patients in both arms

Also known as: Interleukin 6, Interleukin 8, Angiopoeitin-2, soluble-ICAM-1

Airway pressure release ventilation arm; Low-tidal volume ventilation arm

Eligibility Criteria

• Age: 1 Month - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead

Study Sites (1)

Pediatric Intensive care unit, Division of Pediatric Critical Care, Advanced Pediatrics Center, Post-graduate Institute of Medical Education & Research

Chandigarh, 160012, India

Location

Related Publications (6)

• Andrews P, Habashi N. Airway pressure release ventilation. Curr Probl Surg. 2013 Oct;50(10):462-70. doi: 10.1067/j.cpsurg.2013.08.010. No abstract available.

  PMID: 24156844 BACKGROUND

• Andrews PL, Shiber JR, Jaruga-Killeen E, Roy S, Sadowitz B, O'Toole RV, Gatto LA, Nieman GF, Scalea T, Habashi NM. Early application of airway pressure release ventilation may reduce mortality in high-risk trauma patients: a systematic review of observational trauma ARDS literature. J Trauma Acute Care Surg. 2013 Oct;75(4):635-41. doi: 10.1097/TA.0b013e31829d3504.

  PMID: 24064877 BACKGROUND

• Emr B, Gatto LA, Roy S, Satalin J, Ghosh A, Snyder K, Andrews P, Habashi N, Marx W, Ge L, Wang G, Dean DA, Vodovotz Y, Nieman G. Airway pressure release ventilation prevents ventilator-induced lung injury in normal lungs. JAMA Surg. 2013 Nov;148(11):1005-12. doi: 10.1001/jamasurg.2013.3746.

  PMID: 24026214 BACKGROUND

• Roy SK, Emr B, Sadowitz B, Gatto LA, Ghosh A, Satalin JM, Snyder KP, Ge L, Wang G, Marx W, Dean D, Andrews P, Singh A, Scalea T, Habashi N, Nieman GF. Preemptive application of airway pressure release ventilation prevents development of acute respiratory distress syndrome in a rat traumatic hemorrhagic shock model. Shock. 2013 Sep;40(3):210-6. doi: 10.1097/SHK.0b013e31829efb06.

  PMID: 23799354 BACKGROUND

• Roy S, Habashi N, Sadowitz B, Andrews P, Ge L, Wang G, Roy P, Ghosh A, Kuhn M, Satalin J, Gatto LA, Lin X, Dean DA, Vodovotz Y, Nieman G. Early airway pressure release ventilation prevents ARDS-a novel preventive approach to lung injury. Shock. 2013 Jan;39(1):28-38. doi: 10.1097/SHK.0b013e31827b47bb.

  PMID: 23247119 BACKGROUND

• Lalgudi Ganesan S, Jayashree M, Chandra Singhi S, Bansal A. Airway Pressure Release Ventilation in Pediatric Acute Respiratory Distress Syndrome. A Randomized Controlled Trial. Am J Respir Crit Care Med. 2018 Nov 1;198(9):1199-1207. doi: 10.1164/rccm.201705-0989OC.

  PMID: 29641221 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome

Interventions

Continuous Positive Airway Pressure; Methylprednisolone; Interleukin-6; Interleukin-8

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chemokines, CXC; Chemokines; Chemotactic Factors; Inflammation Mediators

Study Officials

• Saptharishi L G, MBBS, MD

  DM (Pediatric Critical Care) Senior Resident, Division of Pediatric critical care, Dept Of Pediatrics, Advanced Pediatrics Center, PGIMER, Chandigarh, INDIA

  PRINCIPAL INVESTIGATOR

• Jayashree Muralidharan, MBBS, MD

  Additional Professor, Division of Pediatric critical care, Dept of Pediatrics, Advanced Pediatrics Center, PGIMER, Chandigarh, India

  STUDY CHAIR

• Sunit C Singhi, MBBS, MD

  Chief, Division of Pediatric Critical Care, Professor & Head, Department of Pediatrics, Advanced Pediatrics Center, PGIMER, Chandigarh, India

  STUDY DIRECTOR

• Arun Bansal, MBBS, MD

  Assistant Professor, Division of Pediatric Critical care, Dept of Pediatrics, Advanced Pediatrics Center, PGIMER, Chandigarh, India

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: DM (Pediatric Critical Care) Senior Resident, Division of Pediatric Critical care, Dept. of Pediatrics

Study Record Dates

• First Submitted: June 16, 2014
• First Posted: June 19, 2014
• Study Start: February 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: December 1, 2016
• Last Updated: May 19, 2017

Record last verified: 2017-05

Locations

IN (1)