Preventive Effects of Penehyclidine Hydrochloride Inhalation on Postoperative Pulmonary Complications

November 1, 2020 updated by: Dong-Xin Wang, Peking University First Hospital

Preventive Effects of Penehyclidine Hydrochloride Inhalation on Postoperative Pulmonary Complications in High-risk Patients: a Randomized, Double-blind, and Placebo Controlled Study

Postoperative pulmonary complications (PPCs) are major causes of postoperative morbidity, mortality, and prolonged hospital stay.The incidence of PPCs may be as high as 41% to 75% in high-risk patients. Bronchodilator is frequently used in high-risk patients to prevent PPCs. Penehyclidine is a new anticholinergic agent which selectively block M1 and M3, but not M2 receptors. A pilot study of the investigators showed that prophylactic penehyclidine inhalation reduced the incidence of bronchospasm and the use of aminophylline in elderly patients after long-duration surgery. The purpose of this study is to investigate whether prophylactically penehyclidine inhalation could decrease the incidence of PPCs in high-risk patients after major intrathoracic and upper intraabdominal surgery.

Study Overview

Detailed Description

Postoperative pulmonary complications (PPCs) are major causes of postoperative morbidity, mortality, and prolonged hospital stay. The incidence of PPCs was found to vary from 2 to 19%, but this rate might be as high as 41 to 75% in patients after intrathoracic and intraabdominal surgery. According to Canet's model, the predicted incidence of PPCs in high-risk patients (ARISCAT risk index >= 45 points) is 42.1%. Use of effective strategies to prevent PPCs is essential for these patients.

Strategies that have been proved to be beneficial in decreasing PPCs include smoking cessation, proper management of chronic obstructive pulmonary disease before surgery, as well as use of lung-protective ventilation and goal-directed fluid therapy during surgery. Besides, bronchodilator inhalation is also helpful. Studies showed that, in high-risk patients undergoing intrathoracic surgery, airway resistance was increased due to bronchial hyperresponsiveness, which increased the risk of PPCs. Inhalation of anticholinergic bronchodilator can reduce the activity of vagus nerve and relieve high airway resistance, which may decrease the risk of bronchospasm and other PPCs.

It has been shown that M1, M3-receptor selective blockers have better effects than β2-receptor activator in dilating bronchia. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (updated 2014) published by Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommend the use of M1, M3-receptor selective blockers to relieve acute exacerbation of chronic obstructive pulmonary disease (COPD) and improve pulmonary function.

Penehyclidine hydrochloride is a new anticholinergic agent, which selectively blocks M1 and M3, but not M2 receptors. Preclinical studies found that it also has anti-inflammation effects. In a pilot study of the investigators, prophylactic inhalation of penehyclidine decreased the incidence of bronchospasm and the use of aminophylline in elderly patients after long-duration surgery. The investigators propose that prophylactic inhalation of penehyclidine might decrease the incidence of PPCs in high risk patients.

The purpose of this study is to investigate whether prophylactic penehyclidine inhalation could decrease the incidence of PPCs in high-risk patients after major intrathoracic and upper intraabdominal surgery.

Study Type

Interventional

Enrollment (Actual)

864

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Beijing
      • Beijing, Beijing, China, 100034
        • Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

51 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age >50 years;
  2. Scheduled to undergo upper abdominal or noncardiac thoracic surgery with expected duration ≥2 hours. For those who undergo laparoscopic or thoracoscopic surgery, the expected length of incision must be ≥5 cm;
  3. Judged to be at high risk of PPCs according to the ARISCAT risk score (ARISCAT predictive score ≥45).

Exclusion Criteria:

  1. American Society of Anesthesiologists (ASA) physical classification ≥IV or the expected survival duration ≤24 hours;
  2. Preoperative history of symptomatic hypertrophy or glaucoma;
  3. History of myocardial infarction, severe heart dysfunction (New York Heart Association functional classification ≥3) or tachyarrhythmia within one year;
  4. Inhalation of β2-receptor activator, M-receptor blockers and/or glucocorticoids within one month before surgery;
  5. Severe renal dysfunction (requirement of renal replacement therapy) or severe hepatic dysfunction (Child-Pugh grade C);
  6. History of acute stroke within three months before surgery;
  7. Refuse to participate in the study or unable to cooperate with the inhalation therapy;
  8. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Penehyclidine group
Penehyclidine inhalation will be administered (penehyclidine hydrochloride 0.5 mg/0.5 ml + normal saline 5.5 ml) once every 12 hours from the night before surgery till the second day after surgery. The total number of inhalation is seven times. Study drug inhalation will be performed with the high-flow oxygen-driven method for the non-intubated patients or with the atomizing inhalation device of ventilator for the intubated patients.
Penehyclidine inhalation will be administered by inhalation (penehyclidine hydrochloride 0.5 mg/0.5 ml, mixed with normal saline 5.5 ml) once every 12 hours from the night before surgery till the second day after surgery. The total number of inhalation is seven times. Study drug inhalation is performed with the high-flow oxygen-driven method for the non-intubated patients or with the atomizing inhalation device of ventilator for the intubated patients.
Other Names:
  • Penehyclidine Hydrochloride for Injection (Changtuoning)
Placebo Comparator: Control group
Placebo inhalation will be administered by inhalation (water for injection 0.5 ml + normal saline 5.5 ml ) once every 12 hours from the night before surgery till the second day after surgery. The total number of inhalation is seven times. Study drug inhalation will be performed with the high-flow oxygen-driven method for the non-intubated patients or with the atomizing inhalation device of ventilator for the intubated patients.
Placebo inhalation will be administered by inhalation (water for injection 0.5 ml, mixed with normal saline 5.5 ml) once every 12 hours from the night before surgery till the second day after surgery. The total number of inhalation is seven times. Study drug inhalation is performed with the high-flow oxygen-driven method for the non-intubated patients or with the atomizing inhalation device of ventilator for the intubated patients.
Other Names:
  • Water for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of postoperative pulmonary complications (PPCs)
Time Frame: Up to 30 days after surgery
PPCs indicate complications that occur in the respiratory system from end of surgery till 30 days after surgery and require therapeutic intervention. Items include respiratory failure, respiratory infection, atelectasis, pleural effusion, bronchospasm, pneumothorax and aspiration pneumonitis.
Up to 30 days after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-cause 30-day mortality
Time Frame: Up to 30 days after surgery
All-cause 30-day mortality
Up to 30 days after surgery
Time to onset of PPCs
Time Frame: From end of surgery till onset of first documented PPCs or death from any cause, whichever came first, assessed up to 30 days
Time to onset of PPCs
From end of surgery till onset of first documented PPCs or death from any cause, whichever came first, assessed up to 30 days
Number of PPCs
Time Frame: Up to 30 days after surgery
Items of PPCs include respiratory infection, atelectasis, pleural effusion, bronchospasm, respiratory failure, pneumothorax and aspiration pneumonitis.
Up to 30 days after surgery
Incidence of extrapulmonary complications
Time Frame: Up to 30 days after surgery
Extrapulmonary complications indicate complications that occurred in the organs or systems other than the respiratory system and require therapeutic intervention.
Up to 30 days after surgery
Length of stay (LOS) in hospital after surgery
Time Frame: Up to 30 days after surgery
Length of stay (LOS) in hospital after surgery
Up to 30 days after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Dong-Xin Wang, MD, PhD, Peking University First Hopital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2015

Primary Completion (Actual)

November 8, 2018

Study Completion (Actual)

December 10, 2018

Study Registration Dates

First Submitted

December 30, 2015

First Submitted That Met QC Criteria

December 31, 2015

First Posted (Estimate)

January 1, 2016

Study Record Updates

Last Update Posted (Actual)

November 3, 2020

Last Update Submitted That Met QC Criteria

November 1, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015[06]
  • ChiCTR-IPC-15006603 (Registry Identifier: Chinese Clinical Trial Registry (www.chictr.org.cn))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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