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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05953649
Other study ID # SYSKY-2023-376-02
Secondary ID
Status Not yet recruiting
Phase N/A
First received
Last updated
Start date August 1, 2023
Est. completion date July 27, 2024

Study information

Verified date May 2023
Source Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Contact Zhijie He
Phone 011-86-13710898290
Email hezhijie@mail.sysu.edu.cn
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The aim of this study is to test the effect of 1week of extracorporeal diaphragm pacing (EDP) combined either with or without tilt table verticalization (TTV) on diaphragm function in patients with mechanical ventilation compared to conventional physiotherapy (CPT).


Description:

In order to explore whether extracorporeal diaphragm pacing (EDP) combined with tilt table verticalization (TTV) improves diaphragm function in mechanically ventilated patients, the investigators conducted a three-arms randomized controlled trial of 90 ventilated patients in the ICU of a general hospital in the southern China state of Guangzhou. After assessment of inclusion and exclusion criteria, patients were randomly assigned to one of the following three groups: (1) EDP with TTV and with conventional physiotherapy (CPT) (n = 30), (2) EDP without TTV and with CPT (n = 30), and (3) conventional physiotherapy (CPT; n = 30).


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 90
Est. completion date July 27, 2024
Est. primary completion date May 27, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 85 Years
Eligibility Inclusion Criteria: - Duration of mechanical ventilation prior to enrollment= 72 hours. - Expected duration of mechanical ventilation=72 hours. - Participants (or their legal representatives) have signed informed consent. Exclusion Criteria: - Pregnancy or breast-feeding. - Prone ventilation or current extracorporeal membrane oxygenation. - Hemodynamic instability: mean arterial pressure is less than 65 millimeters of mercury (mmHg) or higher than 85 millimeters of mercury (mmHg), heart rate > 150 beats / minute, intravenous use of larger doses of vasopressors (such as dopamine > 10 mg/ (kg· min) or norepinephrine/epinephrine >0.1 mg/ (kg· min)) or aortic balloon counter pulsation; respiratory rate< 5 breaths per minute; Oxygen saturation< 88%. - New-onset myocardial ischemia. - Unstable cervical spine fracture and spinal cord injury. - Deterioration of neurological function, requiring intracranial pressure monitoring and ventricular drainage, or active control of intracranial hypertension. - Current neuromuscular block treatment or pre-existing neuromuscular disease or neuromuscular junction disease affecting respiratory muscle (such as myasthenia gravis, Guillain-Barré syndrome, etc.). - There are contraindications to diaphragmatic pacing (local skin, tissue incompleteness or infection, chest X-ray examination shows pneumothorax or pleural effusion accounting for 1/3 of bilateral chest cavity). - Body mass index (BMI) ?40 kg/m2. - Known / suspected phrenic nerve palsy. - Patients who refuse active treatment or are in the terminal stage of malignant tumors, have an expected life expectancy of < 6 months, etc. - Participated in other clinical studies related to mechanical ventilation within 2 months prior to the start of the study.

Study Design


Intervention

Device:
Extracorporeal Diaphragm Pacing
In the EDP group, a pacer using the extracorporeal diaphragm pacemaker provided by Guangzhou Xueliang Biotechnology Developing Co., Ltd., the pacing electrode is pasted on the body surface closest to the phrenic nerve at the outer edge of the lower end of the sternocleidomastoid muscle under ultrasound guidance, and the auxiliary electrode is placed between the second intercostal of the midline of the clavicle. The intensity of treatment parameters was set from low to high, and the intensity of treatment was increased when the patient could tolerate it, pacing 12-18 times/min at a frequency of 40 hertz (Hz)/30min/time, and performed every 12 hours for a week.
Tilt Table Verticalization
VitalGo bed (VitalGo Systems Ltd., Fort Lauderdale) is used for verticalization. Verticalization was set to minimum 30°, depending on cardiopulmonary parameters (respiratory rate, heart rate, blood pressure, oxygen saturation), vertical position was gradually increased (in 5° steps) to a maximum of 90°, as long as the above-named cardiopulmonary parameters of the patient remained stable and remain this position for 30 minutes simultaneously with extracorporeal diaphragm pacing for a week.
Other:
Conventional Physiotherapy
Patients receive early mobilization, which refers to a series of clinical intervention protocols (such as passive movement or active exercises, etc.) that confers physical benefits at an early period in collaboration with a multidisciplinary team (intensive care physicians, rehabilitation physicians, physical therapists, occupational therapists, respiratory therapists, and nurses). The study intervention take place during working time between 8 a.m. and 17 p.m. Patients of all three study groups receive this rehabilitation program until they transfer out of ICU.

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

References & Publications (29)

Aslan GK, Huseyinsinoglu BE, Oflazer P, Gurses N, Kiyan E. Inspiratory Muscle Training in Late-Onset Pompe Disease: The Effects on Pulmonary Function Tests, Quality of Life, and Sleep Quality. Lung. 2016 Aug;194(4):555-61. doi: 10.1007/s00408-016-9881-4. Epub 2016 Apr 22. — View Citation

Berger D, Bloechlinger S, von Haehling S, Doehner W, Takala J, Z'Graggen WJ, Schefold JC. Dysfunction of respiratory muscles in critically ill patients on the intensive care unit. J Cachexia Sarcopenia Muscle. 2016 Sep;7(4):403-12. doi: 10.1002/jcsm.12108. Epub 2016 Mar 9. — View Citation

Brown C, Tseng SC, Mitchell K, Roddey T. Body Position Affects Ultrasonographic Measurement of Diaphragm Contractility. Cardiopulm Phys Ther J. 2018 Oct;29(4):166-172. doi: 10.1097/CPT.0000000000000083. Epub 2018 May 30. — View Citation

Chang AT, Boots RJ, Hodges PW, Thomas PJ, Paratz JD. Standing with the assistance of a tilt table improves minute ventilation in chronic critically ill patients. Arch Phys Med Rehabil. 2004 Dec;85(12):1972-6. doi: 10.1016/j.apmr.2004.03.024. — View Citation

Dong Z, Liu Y, Gai Y, Meng P, Lin H, Zhao Y, Xing J. Early rehabilitation relieves diaphragm dysfunction induced by prolonged mechanical ventilation: a randomised control study. BMC Pulm Med. 2021 Mar 29;21(1):106. doi: 10.1186/s12890-021-01461-2. — View Citation

Dres M, de Abreu MG, Merdji H, Muller-Redetzky H, Dellweg D, Randerath WJ, Mortaza S, Jung B, Bruells C, Moerer O, Scharffenberg M, Jaber S, Besset S, Bitter T, Geise A, Heine A, Malfertheiner MV, Kortgen A, Benzaquen J, Nelson T, Uhrig A, Moenig O, Meziani F, Demoule A, Similowski T; RESCUE-2 Study Group Investigators. Randomized Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients. Am J Respir Crit Care Med. 2022 May 15;205(10):1169-1178. doi: 10.1164/rccm.202107-1709OC. — View Citation

Dres M, Dube BP, Mayaux J, Delemazure J, Reuter D, Brochard L, Similowski T, Demoule A. Coexistence and Impact of Limb Muscle and Diaphragm Weakness at Time of Liberation from Mechanical Ventilation in Medical Intensive Care Unit Patients. Am J Respir Crit Care Med. 2017 Jan 1;195(1):57-66. doi: 10.1164/rccm.201602-0367OC. — View Citation

Dridi H, Yehya M, Barsotti R, Reiken S, Angebault C, Jung B, Jaber S, Marks AR, Lacampagne A, Matecki S. Mitochondrial oxidative stress induces leaky ryanodine receptor during mechanical ventilation. Free Radic Biol Med. 2020 Jan;146:383-391. doi: 10.1016/j.freeradbiomed.2019.11.019. Epub 2019 Nov 19. — View Citation

Frazzitta G, Zivi I, Valsecchi R, Bonini S, Maffia S, Molatore K, Sebastianelli L, Zarucchi A, Matteri D, Ercoli G, Maestri R, Saltuari L. Effectiveness of a Very Early Stepping Verticalization Protocol in Severe Acquired Brain Injured Patients: A Randomized Pilot Study in ICU. PLoS One. 2016 Jul 22;11(7):e0158030. doi: 10.1371/journal.pone.0158030. eCollection 2016. — View Citation

Hearn E, Gosselink R, Freene N, Boden I, Green M, Bissett B. Inspiratory muscle training in intensive care unit patients: An international cross-sectional survey of physiotherapist practice. Aust Crit Care. 2022 Sep;35(5):527-534. doi: 10.1016/j.aucc.2021.08.002. Epub 2021 Sep 8. — View Citation

Hodgson CL, Stiller K, Needham DM, Tipping CJ, Harrold M, Baldwin CE, Bradley S, Berney S, Caruana LR, Elliott D, Green M, Haines K, Higgins AM, Kaukonen KM, Leditschke IA, Nickels MR, Paratz J, Patman S, Skinner EH, Young PJ, Zanni JM, Denehy L, Webb SA. Expert consensus and recommendations on safety criteria for active mobilization of mechanically ventilated critically ill adults. Crit Care. 2014 Dec 4;18(6):658. doi: 10.1186/s13054-014-0658-y. — View Citation

Keogh C, Saavedra F, Dubo S, Aqueveque P, Ortega P, Gomez B, Germany E, Pinto D, Osorio R, Pastene F, Poulton A, Jarvis J, Andrews B, FitzGerald JJ. Non-invasive phrenic nerve stimulation to avoid ventilator-induced diaphragm dysfunction in critical care. Artif Organs. 2022 Oct;46(10):1988-1997. doi: 10.1111/aor.14244. Epub 2022 Apr 12. — View Citation

Klompas M, Li L, Kleinman K, Szumita PM, Massaro AF. Associations Between Ventilator Bundle Components and Outcomes. JAMA Intern Med. 2016 Sep 1;176(9):1277-83. doi: 10.1001/jamainternmed.2016.2427. — View Citation

Levine S, Nguyen T, Taylor N, Friscia ME, Budak MT, Rothenberg P, Zhu J, Sachdeva R, Sonnad S, Kaiser LR, Rubinstein NA, Powers SK, Shrager JB. Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med. 2008 Mar 27;358(13):1327-35. doi: 10.1056/NEJMoa070447. — View Citation

Maes K, Stamiris A, Thomas D, Cielen N, Smuder A, Powers SK, Leite FS, Hermans G, Decramer M, Hussain SN, Gayan-Ramirez G. Effects of controlled mechanical ventilation on sepsis-induced diaphragm dysfunction in rats. Crit Care Med. 2014 Dec;42(12):e772-82. doi: 10.1097/CCM.0000000000000685. — View Citation

Mezidi M, Guerin C. Effects of patient positioning on respiratory mechanics in mechanically ventilated ICU patients. Ann Transl Med. 2018 Oct;6(19):384. doi: 10.21037/atm.2018.05.50. — View Citation

Niel-Weise BS, Gastmeier P, Kola A, Vonberg RP, Wille JC, van den Broek PJ; Bed Head Elevation Study Group. An evidence-based recommendation on bed head elevation for mechanically ventilated patients. Crit Care. 2011;15(2):R111. doi: 10.1186/cc10135. Epub 2011 Apr 11. — View Citation

Powers SK, Hudson MB, Nelson WB, Talbert EE, Min K, Szeto HH, Kavazis AN, Smuder AJ. Mitochondria-targeted antioxidants protect against mechanical ventilation-induced diaphragm weakness. Crit Care Med. 2011 Jul;39(7):1749-59. doi: 10.1097/CCM.0b013e3182190b62. — View Citation

Powers SK, Kavazis AN, Levine S. Prolonged mechanical ventilation alters diaphragmatic structure and function. Crit Care Med. 2009 Oct;37(10 Suppl):S347-53. doi: 10.1097/CCM.0b013e3181b6e760. — View Citation

Pozuelo-Carrascosa DP, Cobo-Cuenca AI, Carmona-Torres JM, Laredo-Aguilera JA, Santacruz-Salas E, Fernandez-Rodriguez R. Body position for preventing ventilator-associated pneumonia for critically ill patients: a systematic review and network meta-analysis. J Intensive Care. 2022 Feb 22;10(1):9. doi: 10.1186/s40560-022-00600-z. — View Citation

Rosenfelder MJ, Helmschrott VC, Willacker L, Einhaupl B, Raiser TM, Bender A. Effect of robotic tilt table verticalization on recovery in patients with disorders of consciousness: a randomized controlled trial. J Neurol. 2023 Mar;270(3):1721-1734. doi: 10.1007/s00415-022-11508-x. Epub 2022 Dec 19. — View Citation

Spooner AJ, Corley A, Sharpe NA, Barnett AG, Caruana LR, Hammond NE, Fraser JF. Head-of-bed elevation improves end-expiratory lung volumes in mechanically ventilated subjects: a prospective observational study. Respir Care. 2014 Oct;59(10):1583-9. doi: 10.4187/respcare.02733. Epub 2014 May 20. — View Citation

Supinski GS, Callahan LA. Diaphragm weakness in mechanically ventilated critically ill patients. Crit Care. 2013 Jun 20;17(3):R120. doi: 10.1186/cc12792. — View Citation

Tang H, Shrager JB. The Signaling Network Resulting in Ventilator-induced Diaphragm Dysfunction. Am J Respir Cell Mol Biol. 2018 Oct;59(4):417-427. doi: 10.1165/rcmb.2018-0022TR. — View Citation

van den Berg M, Hooijman PE, Beishuizen A, de Waard MC, Paul MA, Hartemink KJ, van Hees HWH, Lawlor MW, Brocca L, Bottinelli R, Pellegrino MA, Stienen GJM, Heunks LMA, Wust RCI, Ottenheijm CAC. Diaphragm Atrophy and Weakness in the Absence of Mitochondrial Dysfunction in the Critically Ill. Am J Respir Crit Care Med. 2017 Dec 15;196(12):1544-1558. doi: 10.1164/rccm.201703-0501OC. — View Citation

Vorona S, Sabatini U, Al-Maqbali S, Bertoni M, Dres M, Bissett B, Van Haren F, Martin AD, Urrea C, Brace D, Parotto M, Herridge MS, Adhikari NKJ, Fan E, Melo LT, Reid WD, Brochard LJ, Ferguson ND, Goligher EC. Inspiratory Muscle Rehabilitation in Critically Ill Adults. A Systematic Review and Meta-Analysis. Ann Am Thorac Soc. 2018 Jun;15(6):735-744. doi: 10.1513/AnnalsATS.201712-961OC. — View Citation

Wang L, Li X, Yang Z, Tang X, Yuan Q, Deng L, Sun X. Semi-recumbent position versus supine position for the prevention of ventilator-associated pneumonia in adults requiring mechanical ventilation. Cochrane Database Syst Rev. 2016 Jan 8;2016(1):CD009946. doi: 10.1002/14651858.CD009946.pub2. — View Citation

Yang X, Zhang T, Cao L, Ye L, Song W. Early Mobilization for Critically Ill Patients. Respir Care. 2023 Jun;68(6):781-795. doi: 10.4187/respcare.10481. Epub 2023 Apr 11. — View Citation

Zergeroglu MA, McKenzie MJ, Shanely RA, Van Gammeren D, DeRuisseau KC, Powers SK. Mechanical ventilation-induced oxidative stress in the diaphragm. J Appl Physiol (1985). 2003 Sep;95(3):1116-24. doi: 10.1152/japplphysiol.00824.2002. Epub 2003 May 30. — View Citation

* Note: There are 29 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Other Day 28 mortality Short-term mortality was defined as a date of all-cause death within 28 days of the finishing of the trial. within 28 days of the finishing of the trial.
Other ventilator free days It is defined as a date of no ventilation within 28 days of the start of the trial. within 28 days of the start of the trial
Other Length of stay in ICU The patient's length of stay in the ICU since the beginning of inclusion. up to 28 days.
Other Ratio of short weaning It is defined as the first separation attempt resulted in a termination of the weaning process within 24 hours (successful separation or early death). within 28 days of the start of the trial
Other Duration of control ventilation It is defined as the ventilation mode in which the frequency, tidal volume, and inspiratory time of breathing are controlled by a ventilator because the patient has no spontaneous breathing or very weak spontaneous breathing. within 28 days of the start of the trial
Other Duration of ventilation It is defined as a date of ventilation within 28 days of the start of the trial. within 28 days of the start of the trial
Primary Change from Baseline on Diaphragm Thickening Fraction at Day 4 and Day 7. The Diaphragm thickening fraction-DTf (%) was calculated as the difference between end-expiration and end-inspiration divided by end-inspiration × 100.Diaphragm thickening fraction (DTf) less than 20% is a measure of ultrasonographic diaphragmatic dysfunction in patients on mechanical ventilation. Baseline, Day 4 and Day 7.
Secondary Change from Baseline on Ventilation mode at Day 4 and Day 7. A ventilator mode is a way of describing how the mechanical ventilator assists the patient with taking a breath. Baseline, Day 4 and Day 7.
Secondary Change from Baseline on Positive End-expiratory Pressure (PEEP) at Day 4 and Day 7. Positive end-expiratory pressure (PEEP) is the positive pressure that will remain in the airways at the end of the respiratory cycle (end of exhalation) that is greater than the atmospheric pressure in mechanically ventilated patients. Baseline, Day 4 and Day 7.
Secondary Change from Baseline on minute ventilation at Day 4 and Day 7. It usually refers to the expired amount and can be calculated using the following equation: minute ventilation (VE)= tidal volume (VT) ×respiratory frequency(f) Baseline, Day 4 and Day 7.
Secondary Change from Baseline on tidal volume at Day 4 and Day 7. Tidal volume is the amount of air that moves in or out of the lungs with each respiratory cycle. Baseline, Day 4 and Day 7.
Secondary Change from Baseline on Maximum Inspiratory Pressure (MIP) at Day 4 and Day 7. The maximum inspiratory pressures measure the maximal efforts of the respiratory muscles. Baseline, Day 4 and Day 7.
Secondary Change from Baseline on airway occlusion pressure (P0.1) at Day 4 and Day 7. P0.1 is a parameter for the neuro-muscular activation of the respiratory system, which is an important determinant for the work of breathing. Baseline, Day 4 and Day 7.
Secondary Change from Baseline on transdiaphragmatic pressure at Day 4 and Day 7. Transdiaphragmatic pressure (Pdi) represents the pressure across the diaphragm, which can be expressed as the difference between abdominal pressure (Pab) and pleural pressure (Ppl):Pdi = Ppl- Pab. Baseline, Day 4 and Day 7.
Secondary Change from Baseline on MRC score at Day 4 and Day 7. Medical Research Council (MRC)-sum score evaluates global muscle strength. Manual strength of six muscle groups (shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion) is evaluated on both sides using MRC scale. Summation of scores gives MRC-sum score, ranging from 0 to 60. Baseline, Day 4 and Day 7.
Secondary Change from Baseline on Blood oxygen status at Day 4 and Day 7. Oxygenation Index = (FiO2× Mean Airway Pressure) / partial pressure of oxygen in arterial blood (PaO2) The oxygenation index is used to assess the intensity of ventilatory support required to maintain oxygenation. Baseline, Day 4 and Day 7.
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