Prophylactic Penehyclidine Hydrochloride Inhalation and 3-year Outcome After Surgery

NCT ID: NCT03868709

Last Updated: 2025-04-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

864 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-12

Study Completion Date

2021-12-01

Brief Summary

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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 receptors. A previous randomized controlled trial tested the effect of prophylactic penehyclidine inhalation on the incidence of PPCs in high-risk patients. The purpose of this 3-year follow-up study is to investigate whether prophylactically penehyclidine hydrochloride inhalation can affect the 3-year outcomes of patients recruited in the previous randomized controlled trial.

Detailed Description

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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 may 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 those high-risk patients. As a bronchodilator, anticholinergic inhalation may be helpful. Studies showed that, in high-risk patients undergoing intrathoracic surgery, airway resistance is 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.

Penehyclidine hydrochloride is a new anticholinergic agent, which selectively blocks M1 and M3 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. In a previous randomized controlled trial, 864 high-risk patients were recruited and randomized to receive prophylactic inhalation of either penehyclidine or placebo.

The investigators hypothesize that prophylactically penehyclidine hydrochloride inhalation may improve long-term outcomes in this patient population by reducing PPCs. The purpose of this 3-year follow-up study is to investigate whether prophylactically penehyclidine hydrochloride inhalation can affect the 3-year outcomes in high-risk patients recruited in the previous randomized controlled trial.

Conditions

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Postoperative Complications Long-term Outcome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Penehyclidine group

Penehyclidine inhalation is 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 is performed with the high-flow oxygendriven method for the non-intubated patients or with the atomizing inhalation device of ventilator for the intubated patients.

Group Type EXPERIMENTAL

Penehyclidine inhalation

Intervention Type DRUG

Penehyclidine inhalation is 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

Placebo group

Placebo inhalation is 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.

Group Type PLACEBO_COMPARATOR

Placebo inhalation

Intervention Type DRUG

Placebo inhalation is 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 oxygendriven method for the non-intubated patients or with the atomizing inhalation device of ventilator for the intubated patients.

Interventions

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Penehyclidine inhalation

Penehyclidine inhalation is 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

Intervention Type DRUG

Placebo inhalation

Placebo inhalation is 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 oxygendriven method for the non-intubated patients or with the atomizing inhalation device of ventilator for the intubated patients.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age of 50 years or over;
2. Scheduled to undergo open or laparoscope assisted upper abdominal or intrathoracic surgery;
3. The expected duration of surgery is 2 hours or longer;
4. Identified 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 h;
2. Preoperative history of prostatic 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.
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Peking University First Hospital

OTHER

Sponsor Role lead

Responsible Party

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Dong-Xin Wang

Professor and Chairman, Department of Anesthesiology and Critical Care Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Dong-Xin Wang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Peking University First Hospital

Locations

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Peking University First Hospital

Beijing, Beijing Municipality, China

Site Status

Countries

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China

References

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Other Identifiers

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2018[213]

Identifier Type: -

Identifier Source: org_study_id

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