Clinical trial NCT03868709: Prophylactic Penehyclidine Hydrochloride Inhalation and 3-year Outcome After Surgery
Official title: Impact of Prophylactic Penehyclidine Hydrochloride Inhalation on Long-term Outcome in High-risk Patients: 3-year Follow-up of a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Postoperative Complications
Long-term Outcome
Keywords: Postoperative pulmonary complications
Penehyclidine Hydrochloride
High risk patients
Postoperative period
Long-term outcome
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
First posted: 2019-03-11
Enrollment: 864
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Duration of overall survival within 3 years after surgery
timeFrame: From the day of surgery until the end of the 3rd year after surgery
Secondary outcomes:
measure: Survival rates at different timepoints after surgery
timeFrame: At the end of the 1st, 2nd, and 3rd year after surgery
measure: Duration of recurrence-free survival within 3 years after surgery
timeFrame: From the day of surgery until the end of the 3rd year after surgery
measure: Ocurrence of new-onset diseases during the 3-year period after surgery
timeFrame: From the day of surgery until the end of the 3rd year after surgery
measure: Cognitive function of 3-year survivors
timeFrame: Assessed at the end of the 3rd year after surgery
measure: The quality of life in 3-year survivors
timeFrame: Assessed at the end of the 3rd year after surgery
measure: The quality of life in 3-year survivors with chronic pulmonary disease
timeFrame: Assessed at the end of the 3rd year after surgery
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
Study officials:
affiliation: Peking University First Hospital
name: Dong-Xin Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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