Clinical trial NCT06404294: The External Diaphragm Pacemaker Assisted Extubation in Premature Infants With Invasive Mechanical Ventilation
Official title: A Randomized Controlled Study of the External Diaphragm Pacemaker Assisted Extubation in Premature Infants With Invasive Mechanical Ventilation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Invasive Mechanical Ventilation
Extubation
Keywords: External Diaphragm Pacemaker
Invasive Mechanical Ventilation
Extubation
Preterm Infants
Lead sponsor: Children's Hospital of Chongqing Medical University
Sponsor class: OTHER
First posted: 2024-05-08
Enrollment: 40
Sex: ALL
Minimum age (years): 1
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: With the development of perinatal medicine, more and more newborns with respiratory failure can be treated due to the use of respiratory support technology. However, long-term invasive mechanical ventilation treatment can lead to a series of complications such as ventilator-associated pneumonia, atelectasis and air leakage syndrome, and increase the risk of bronchopulmonary dysplasia and neurodevelopmental lag of premature infants. It also leads to longer hospital stays and higher hospital costs. To shorten the invasive mechanical ventilation time and improve the success rate of withdrawal through various ways is the development direction of neonatal mechanical ventilation therapy.

Respiratory muscle atrophy is common and rapid in children receiving invasive mechanical ventilation, and is an important cause of ventilator dependence and withdrawal failure. The diaphragm of newborns is the main respiratory muscle, of which the diaphragm type 1 endurance fiber accounts for only about 30%, far lower than the proportion of about 55% in adults, so the diaphragm of newborns is more prone to fatigue. Previous animal experiments and clinical studies in children and adults have confirmed that diaphragmatic pacing therapy applied to patients with long-term invasive mechanical ventilation can prevent diaphragmatic atrophy, reverse diaphragmatic injury, significantly improve diaphragmatic thickness, improve diaphragmatic anti-fatigue ability, thereby increasing lung ventilation, relieving dyspnea, and achieving the effect of assisted extubation.

The neonatology Department of the Children's Hospital Affiliated to Chongqing Medical University started neonatal external diaphragm pacemaker treatment in 2022, and has completed 1383 cases so far, initially showing the effectiveness and safety of external diaphragm pacemaker treatment in neonatal population. But so far, there is no systematic evaluation of clinical intervention effect of external diaphragm pacemaker treatment on neonatal respiratory failure patients at home and abroad. Based on this, the project team intends to conduct a prospective randomized controlled study to systematically evaluate the safety of external diaphragm pacemaker in preterm infants requiring invasive mechanical ventilation for ≥7 days at 28 to 35 weeks of gestation, and to evaluate the efficacy of external diaphragm pacemaker in adjuvant extubation.

Detailed description: Neonatal respiratory failure is the central or peripheral respiratory dysfunction caused by various reasons, and is an important clinical critical disease of newborns. With the development of perinatal medicine, more and more newborns with respiratory failure can be treated due to the use of respiratory support technology. However, long-term invasive mechanical ventilation treatment can lead to a series of complications such as ventilator-associated pneumonia, atelectasis and air leakage syndrome, and increase the risk of bronchopulmonary dysplasia and neurodevelopmental lag of premature infants. It also leads to longer hospital stays and higher hospital costs. To shorten the invasive mechanical ventilation time and improve the success rate of withdrawal through various ways is the development direction of neonatal mechanical ventilation therapy.

Respiratory muscle atrophy is common and rapid in children receiving invasive mechanical ventilation, and is an important cause of ventilator dependence and withdrawal failure. The diaphragm of newborns is the main respiratory muscle, of which the diaphragm type 1 endurance fiber accounts for only about 30%, far lower than the proportion of about 55% in adults, so the diaphragm of newborns is more prone to fatigue. Studies have shown that phrenic atrophy usually begins within 18-69 hours of invasive mechanical ventilation and progresses at a rate of 4-7% per day.

Previous animal experiments and clinical studies in children and adults have confirmed that diaphragmatic pacing therapy applied to patients with long-term invasive mechanical ventilation can prevent diaphragmatic atrophy, reverse diaphragmatic injury, significantly improve diaphragmatic thickness, improve diaphragmatic anti-fatigue ability, thereby increasing lung ventilation, relieving dyspnea, and achieving the effect of assisted extubation.

In February 1987, the external diaphragm pacemaker independently developed by Chen et al at Sun Yat-sen University of Medical Science was applied to clinical practice, setting a precedent for external diaphragmatic pacing at home and abroad. The basic principle is to perform low-frequency pulse electrical stimulation of the phrenic nerve through the electrodes on the body surface to make the regular contraction and relaxation of the diaphragm and increase the degree of movement of the diaphragm, so as to improve the ventilation function of the patient. In China, Cai et al observed that external diaphragm pacemaker can increase the degree of immediate diaphragm movement in normal people, and significantly increase the degree of immediate movement in patients with chronic obstructive pulmonary disease and the range of diaphragm movement after continuous treatment for 20-30 days, and significantly improve the symptoms of dyspnea.

The neonatology Department of the Children's Hospital Affiliated to Chongqing Medical University started neonatal external diaphragm pacemaker treatment in 2022, and has completed 1383 cases so far, initially showing the effectiveness and safety of external diaphragm pacemaker treatment in neonatal population. But so far, there is no systematic evaluation of clinical intervention effect of external diaphragm pacemaker treatment on neonatal respiratory failure patients at home and abroad. Based on this, the project team intends to conduct a prospective randomized controlled study to systematically evaluate the safety of external diaphragm pacemaker in preterm infants requiring invasive mechanical ventilation for ≥7 days at 28 to 35 weeks of gestation, and to evaluate the efficacy of external diaphragm pacemaker in adjuvant extubation.

Eligibility criteria: Inclusion Criteria:

1. Premature infants at 28 to 35 weeks.
2. The premature infant whose invasive mechanical ventilation time ≥7 days.
3. Parents sign an informed consent form.

Exclusion Criteria:

1. The premature infant with congenital airway malformation confirmed by chest CT or bronchofiberscopy.
2. The premature infant with congenital genetic metabolic disease.
3. The premature infant with complex congenital heart disease.
4. The premature infant undergoing surgery.
5. The premature infant with severe brain damage.
6. The premature infant with neuromuscular diseases.
7. The premature infant with congenital skin disease, local skin damage or infection.

Primary outcomes:
measure: Invasive mechanical ventilation time
timeFrame: through study completion, up to 100 days of life
Secondary outcomes:
measure: Diaphragm geometry and function
timeFrame: through study completion, up to 100 days of life
measure: Duration of oxygen use
timeFrame: through study completion, up to 100 days of life
measure: Incidence of bronchopulmonary dysplasia
timeFrame: through study completion, up to 100 days of life
measure: Mortality
timeFrame: through study completion, up to 100 days of life
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Children's hospital of Chongqing Medical University
state: Chongqing
Study officials:
affiliation: Children's Hospital of Chongqing Medical University
name: Yuan Shi, M.D
role: STUDY_DIRECTOR
References:
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