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Respiratory HypersensitivityPhase 4PEPSINCT06624696

Inhaling Penehyclidine to Prevent Perioperative Respiratory Adverse Events in Children at Risk Undergoing Sevoflurane Anesthesia

A Phase 4 study testing Penehyclidine hydrochloride and Normal Saline in people with Respiratory Hypersensitivity and Perioperative Respiratory Adverse Events, run by Sun Yat-sen University at 2 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This randomized controlled study is to evaluate the effectiveness of inhaling penehyclidine hydrochloride in reducing perioperative respiratory adverse events in children at risk undergoing minor elective surgery. Read more about this study

Who is it for?
Ages 3 to 7 years
What is being tested?
Penehyclidine hydrochloride and Normal Saline
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
204 participants
Where
2 sitesChina
Study dates
12 Nov 2024to 18 Aug 2026
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 7 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Pediatric patients aged 3 to 7 years.
  • Scheduled to undergo ophthalmic surgery.
  • Judged to be at risk of PRAEs (with at least one parentally reported risk factor for the PRAEs, including history of a recent cold, wheezing during exercise, wheezing more than three times in the past 12 months, nocturnal dry cough, eczema, or a family history of asthma, rhinitis, eczema, or exposure to passive smoke).

Who cannot join

  • American Society of Anesthesiologists (ASA) physical classification ≥ IV.
  • Known cardiopulmonary diseases (eg. uncorrected congenital heart disease, primary or secondary pulmonary hypertension, tumors, or structural lung diseases).
  • Severe renal dysfunction (requirement of renal replacement therapy) or severe hepatic dysfunction (Child-Pugh grade C);
  • Neurological disorders.
  • Neuromuscular diseases.
  • Contraindication for PHC.
Show all 14Show fewer
  • Inhalation of β2-receptor activator, M-receptor blockers and/or glucocorticoids within 1 month before surgery.
  • Allergy to anticholinergic drugs.
  • Use of endotracheal tube (ETT) for ventilation.
  • Known difficult airway.
  • Severe upper respiratory tract infections (URTIs) and the anesthesiologist recommended delaying surgery.
  • Participation in other clinical trial during the last month or within the six half-life periods of the study drug used in the last trial.
  • Parents refusing to allow their children to participate.
  • Obesity, with a body mass index (BMI) over 95th percentile according to the WHO guideline.

Trial locations and contacts

2 sites in 1 country.

China2 sites

  • Zhongshan Ophthalmic Center, Sun Yat-sen University

    Guangzhou, Guangdong, 510060

  • Shenzhen Eye Hospital

    Shenzhen, Guangdong, 518040

Other trials in China

About this study

Official title: Inhaling Penehyclidine to Prevent Perioperative Respiratory Adverse Events in Children at Risk Undergoing Sevoflurane Anesthesia: a Double-blind, Randomized, Placebo-controlled Trial

This randomized controlled study is to evaluate the effectiveness of inhaling penehyclidine hydrochloride in reducing perioperative respiratory adverse events in children at risk undergoing minor elective surgery.

Read the detailed description

Children with high risk factors of perioperative respiratory adverse events (PRAEs) remains a challenge for general anesthesia, inhalation of penehyclidine hydrochloride (PHC) has been showed to reduce postoperative pulmonary complications and enhance the recovery in high-risk surgical patients. Thus, prophylactic PHC inhalation might show promising benefits against PRAEs in pediatric anesthesia. This clinical study is designed to test the hypothesis that pediatric patients who exist at least 1 risk factor of PRAEs prophylactically to inhale PHC have a lower prevalence of PRAEs.

Being tested
Penehyclidine hydrochloride, Normal Saline
Keywords
perioperative respiratory adverse events, pediatric anesthesia, penehyclidine, sevoflurane
Medical subject headings
Respiratory Hypersensitivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Penehyclidine hydrochlorideDrug

    The penehyclidine hydrochloride will be diluted to a total volume of 5 mL with normal saline, added to the nebulizer cup for inhalation. Patients will be asked to inhale the entire volume of nebulized drugs within 30 min prior to surgery. The trial drugs will be administered using a jet nebulizer with compressed air flow. Each child will be intructed to begin the nebulization by using a face mask that covers the nose and mouth while the child is seated upright. Children will be encouraged to take deep and slow breaths, inhaling through the mouth and exhaling through the nose, to ensure the drugs effectively reaches the airway.

  • Normal SalineDrug

    The normal saline with a total volume of 5 mL will be added to the nebulizer cup for inhalation. Patients will be asked to inhale the entire volume of nebulized drugs within 30 min prior to surgery. The trial drugs will be administered using a jet nebulizer with compressed air flow. Each child will be intructed to begin the nebulization by using a face mask that covers the nose and mouth while the child is seated upright. Children will be encouraged to take deep and slow breaths, inhaling through the mouth and exhaling through the nose, to ensure the drugs effectively reaches the airway.

Study groups in NCT06624696
Study groupRoleWhat they receive
The penehyclidine hydrochloride groupExperimentalInhaling penehyclidine hydrochloride (a dose of 0.05 mg/kg, diluted and mixed with normal saline to a total volume of 5 ml) for nebulization therapy within 30 min prior to surgery.
Receives: Drug: Penehyclidine hydrochloride
The normal saline groupPlacebo comparatorInhaling normal saline in a total volume of 5 ml for nebulization therapy within 30 min prior to surgery.
Receives: Drug: Normal Saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The incidence of PRAEs

    PRAEs are subdivided into two types: major (bronchospasm and laryngospasm) and minor (severe coughing, breath holding, desaturation, upper airway obstruction, and stridor) events. The primary outcome is the incidence of PRAEs. Patients will be considered positive for respiratory adverse events if at least 1 of the above adverse events occurs.

    Measured: From beginning of anesthesia induction until the completion of postoperative recovery in PACU (including the phases of anesthesia induction, anesthesia maintenance, postoperative emergency and postoperative recovery), assessed up to 24 hours.

Secondary outcomes (12)

  1. The severity of major respiratory adverse events if occurs

    Major respiratory adverse events include laryngospasm and bronchospasm. Laryngospasm will be scored according to its severity as follows: 1=none, 2=partial-reposition airway, 3=partial-continuous positive airway pressure (CPAP), 4=complete-muscle relaxant. Bronchospasm will be scored according to its severity as follows: 1=none, 2= expiration only, 3= expiration and inspiration, 4=difficult to ventilate, require treatment.

    Measured: From beginning of anesthesia induction until the completion of postoperative recovery in PACU (including the phases of anesthesia induction, anesthesia maintenance, postoperative emergency and postoperative recovery), assessed up to 24 hours.

  2. Ease of LMA insertion

    This outcome includes time to successful insertion, the number of insertion attempts, and difficulty at insertion.

    Measured: From the beginning of LMA insertion until the completion of successful LMA insertion, assessed up to 24 hours

  3. The episode and degree of salivation during removal of LMA

    Degree of salivation is evaluated as follows: 1=none; 2=minimal, no suction; 3=moderate, suction 1×; 4=copious, suction>1×.

    Measured: At the time of LMA removal, assessed up to 24 hours

  4. The airway hyperreactivity score

    This score is used to assessed severity of PRAEs, accounting for the intensity of coughing, breath holding, and oxygen desaturation on a scale ranging from 0 (none) to 4 (severe). The maximum score is 12, and a score of ≤3 is categorized as mild, 4 to 8 as moderate, and ≥9 as severe.

    Measured: From the time of LMA removal until regaining consciousness from anesthesia, assessed up to 24 hours

  5. The anesthesia-related time

    The anesthesia-related time includes time to LMA removal, and PACU stay time.

    Measured: During the phases of anesthesia emergence and recovery, assessed up to 24 hours

  6. Emergence agitation

    Emergence agitation will be evaluated within stay in PACU using the Aono's four point scale (1: calm; 2: not calm but easily consolable; 3: not easily calmed restless or moderately agitated; 4: combative, disoriented, or excited). The scale scoring of 1 and 2 are considered as the absence of EA, and scale of 3 and 4 are considered as the presence of EA.

    Measured: From the time of LMA removal until regaining consciousness from anesthesia, assessed up to 24 hours

  7. Postoperative pain score

    Postoperative pain score will be assessed within stay in the PACU using the Wong-Baker Pain Scale. A score higher than 4 is defined as moderate-to-severe pain which need to be timely managed.

    Measured: From the time of arrival in PACU until the time of discharge from PACU, assessed up to 24 hours

  8. The change of systolic blood pressure (SBP)

    The changes of SBP will be recorded.

    Measured: At baseline; 5 minutes after inhaling PHC; the completion of inhaling PHC; LMA insertion; upon arrival in PACU; pre-LMA mask removal; post-LMA mask removal; ready to discharge from PACU, assessed up to 24 hours

  9. The change of heart rate (HR)

    The changes of HR will be recorded.

    Measured: At baseline; 5 minutes after inhaling PHC; the completion of inhaling PHC; LMA insertion; upon arrival in PACU; pre-LMA mask removal; post-LMA mask removal; ready to discharge from PACU, assessed up to 24 hours

  10. The change of SpO2

    The change of SpO2 will be recorded.

    Measured: At baseline; 5 minutes after inhaling PHC; the completion of inhaling PHC; LMA insertion; upon arrival in PACU; pre-LMA mask removal; post-LMA mask removal; ready to discharge from PACU, assessed up to 24 hours

  11. Other adverse events

    Other adverse events potentially related to inhale the study drug from beginning of inhalation until the 24 postoperative hours, including postoperative nausea and vomitting (PONV), dry month, palpation, dizziness, fever, cough, urine retention, and flushing.

    Measured: From beginning of inhalation until the 24 postoperative hours.

  12. The incidence of respiratory infections within 7 days after surgery

    Children who develop respiratory infections within 7 days after surgery will be recorded during postoperative follow-up.

    Measured: Within 7 days after surgery.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Oct 2024
  2. Study start12 Nov 2024
  3. Primary completion11 Aug 2026
  4. Study completion18 Aug 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
204 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06624696
Sponsor's protocol ID
IIT2024111
Acronym
PEPSI
Status last verified
Sep 2026
First submitted
30 Sep 2024
Last updated
2 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Tait AR, Malviya S, Voepel-Lewis T, Munro HM, Seiwert M, Pandit UA. Risk factors for perioperative adverse respiratory events in children with upper respiratory tract infections. Anesthesiology. 2001 Aug;95(2):299-306. doi: 10.1097/00000542-200108000-00008.

    PubMed 11506098

  • Ramgolam A, Hall GL, Sommerfield D, Slevin L, Drake-Brockman TFE, Zhang G, von Ungern-Sternberg BS. Premedication with salbutamol prior to surgery does not decrease the risk of perioperative respiratory adverse events in school-aged children. Br J Anaesth. 2017 Jul 1;119(1):150-157. doi: 10.1093/bja/aex139.

    PubMed 28974069

  • Tait AR, Voepel-Lewis T, Burke C, Kostrzewa A, Lewis I. Incidence and risk factors for perioperative adverse respiratory events in children who are obese. Anesthesiology. 2008 Mar;108(3):375-80. doi: 10.1097/ALN.0b013e318164ca9b.

    PubMed 18292674

  • An MZ, Xu CY, Hou YR, Li ZP, Gao TS, Zhou QH. Effect of intravenous vs. inhaled penehyclidine on respiratory mechanics in patients during one-lung ventilation for thoracoscopic surgery: a prospective, double-blind, randomised controlled trial. BMC Pulm Med. 2023 Sep 19;23(1):353. doi: 10.1186/s12890-023-02653-8.

    PubMed 37726724

  • Yan T, Liang XQ, Wang GJ, Wang T, Li WO, Liu Y, Wu LY, Yu KY, Zhu SN, Wang DX, Sessler DI. Prophylactic Penehyclidine Inhalation for Prevention of Postoperative Pulmonary Complications in High-risk Patients: A Double-blind Randomized Trial. Anesthesiology. 2022 Apr 1;136(4):551-566. doi: 10.1097/ALN.0000000000004159.

    PubMed 35226725

  • Wang NA, Su Y, Che XM, Zheng H, Shi ZG. Penehyclidine ameliorates acute lung injury by inhibiting Toll-like receptor 2/4 expression and nuclear factor-kappaB activation. Exp Ther Med. 2016 May;11(5):1827-1832. doi: 10.3892/etm.2016.3154. Epub 2016 Mar 11.

    PubMed 27168812

  • Wang Y, Gao Y, Ma J. Pleiotropic effects and pharmacological properties of penehyclidine hydrochloride. Drug Des Devel Ther. 2018 Oct 5;12:3289-3299. doi: 10.2147/DDDT.S177435. eCollection 2018.

    PubMed 30323561

  • Tait AR, Burke C, Voepel-Lewis T, Chiravuri D, Wagner D, Malviya S. Glycopyrrolate does not reduce the incidence of perioperative adverse events in children with upper respiratory tract infections. Anesth Analg. 2007 Feb;104(2):265-70. doi: 10.1213/01.ane.0000243333.96141.40.

    PubMed 17242078

  • Wudineh DM, Berhe YW, Chekol WB, Adane H, Workie MM. Perioperative Respiratory Adverse Events Among Pediatric Surgical Patients in University Hospitals in Northwest Ethiopia; A Prospective Observational Study. Front Pediatr. 2022 Feb 11;10:827663. doi: 10.3389/fped.2022.827663. eCollection 2022.

    PubMed 35223702

  • Ramgolam A, Hall GL, Zhang G, Hegarty M, von Ungern-Sternberg BS. Deep or awake removal of laryngeal mask airway in children at risk of respiratory adverse events undergoing tonsillectomy-a randomised controlled trial. Br J Anaesth. 2018 Mar;120(3):571-580. doi: 10.1016/j.bja.2017.11.094. Epub 2018 Jan 27.

    PubMed 29452814

  • von Ungern-Sternberg BS, Sommerfield D, Slevin L, Drake-Brockman TFE, Zhang G, Hall GL. Effect of Albuterol Premedication vs Placebo on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomies: The REACT Randomized Clinical Trial. JAMA Pediatr. 2019 Jun 1;173(6):527-533. doi: 10.1001/jamapediatrics.2019.0788.

    PubMed 31009034

  • Peterson MB, Gurnaney HG, Disma N, Matava C, Jagannathan N, Stein ML, Liu H, Kovatsis PG, von Ungern-Sternberg BS, Fiadjoe JE; PAWS-COVID-19 Group. Complications associated with paediatric airway management during the COVID-19 pandemic: an international, multicentre, observational study. Anaesthesia. 2022 Jun;77(6):649-658. doi: 10.1111/anae.15716. Epub 2022 Mar 23.

    PubMed 35319088

  • Oofuvong M, Geater AF, Chongsuvivatwong V, Chanchayanon T, Sriyanaluk B, Saefung B, Nuanjun K. Excess costs and length of hospital stay attributable to perioperative respiratory events in children. Anesth Analg. 2015 Feb;120(2):411-9. doi: 10.1213/ANE.0000000000000557.

    PubMed 25517194

  • Hii J, Templeton TW, Sommerfield D, Sommerfield A, Matava CT, von Ungern-Sternberg BS. Risk assessment and optimization strategies to reduce perioperative respiratory adverse events in pediatric anesthesia-Part 1 patient and surgical factors. Paediatr Anaesth. 2022 Feb;32(2):209-216. doi: 10.1111/pan.14377. Epub 2021 Dec 20.

    PubMed 34897906

  • Shen F, Zhang Q, Xu Y, Wang X, Xia J, Chen C, Liu H, Zhang Y. Effect of Intranasal Dexmedetomidine or Midazolam for Premedication on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial. JAMA Netw Open. 2022 Aug 1;5(8):e2225473. doi: 10.1001/jamanetworkopen.2022.25473.

    PubMed 35943745

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Penehyclidine hydrochloride and Normal Saline in people with Respiratory Hypersensitivity and Perioperative Respiratory Adverse Events, run by Sun Yat-sen University at 2 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The incidence of PRAEs (time frame: From beginning of anesthesia induction until the completion of postoperative recovery in PACU (including the phases of anesthesia induction, anesthesia maintenance, postoperative emergency and postoperative recovery), assessed up to 24 hours.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06624696, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.

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