Prophylactic Penehyclidine Hydrochloride Inhalation and 3-year Outcome After Surgery

Postoperative Complications Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03868709
• Other study ID #: 2018[213]
• Status: Completed
• Phase: Phase 4
• Start date: November 10, 2018
• Est. completion date: December 1, 2021

Study information

• Verified date: April 2022
• Source: Peking University First Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 864
• Est. completion date: December 1, 2021
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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 ß2-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.

Related Conditions & MeSH terms

• Long-term Outcome
• Postoperative Complications

Intervention

Drug:
• 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
• 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.

Locations

Country	Name	City	State
China	Peking University First Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University First Hospital

Country where clinical trial is conducted

China, 

References & Publications (19)

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Canet J, Gallart L, Gomar C, Paluzie G, Vallès J, Castillo J, Sabaté S, Mazo V, Briones Z, Sanchis J; ARISCAT Group. Prediction of postoperative pulmonary complications in a population-based surgical cohort. Anesthesiology. 2010 Dec;113(6):1338-50. doi: 10.1097/ALN.0b013e3181fc6e0a. — View Citation

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Melduni RM, Koshino Y, Shen WK. Management of arrhythmias in the perioperative setting. Clin Geriatr Med. 2012 Nov;28(4):729-43. doi: 10.1016/j.cger.2012.08.006. Review. — View Citation

Ramachandran SK, Nafiu OO, Ghaferi A, Tremper KK, Shanks A, Kheterpal S. Independent predictors and outcomes of unanticipated early postoperative tracheal intubation after nonemergent, noncardiac surgery. Anesthesiology. 2011 Jul;115(1):44-53. doi: 10.1097/ALN.0b013e31821cf6de. — View Citation

Sabaté S, Mazo V, Canet J. Predicting postoperative pulmonary complications: implications for outcomes and costs. Curr Opin Anaesthesiol. 2014 Apr;27(2):201-9. doi: 10.1097/ACO.0000000000000045. Review. — View Citation

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Wu GM, Mou M, Mo LQ, Liu L, Ren CH, Chen Y, Zhou J. Penehyclidine hydrochloride postconditioning on lipopolysaccharide-induced acute lung injury by inhibition of inflammatory factors in a rodent model. J Surg Res. 2015 May 1;195(1):219-27. doi: 10.1016/j.jss.2014.12.018. Epub 2014 Dec 17. — View Citation

Yan T, Wang D. [Effects of penehyclidine inhalation on postoperative pulmonary complications of elderly patients after long-duration surgery]. Zhonghua Yi Xue Za Zhi. 2014 Jan 14;94(2):122-6. Chinese. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of overall survival within 3 years after surgery	Duration of overall survival within 3 years after surgery	From the day of surgery until the end of the 3rd year after surgery
Secondary	Survival rates at different timepoints after surgery	Survival rates at different timepoints after surgery	At the end of the 1st, 2nd, and 3rd year after surgery
Secondary	Duration of recurrence-free survival within 3 years after surgery	Duration of recurrence-free survival within 3 years after surgery for primary cancer	From the day of surgery until the end of the 3rd year after surgery
Secondary	Ocurrence of new-onset diseases during the 3-year period after surgery	New-onset diseases indicate those that occurred during the 3-year period after surgery and required medical therapy, such as acute myocardial infarction, stroke, new cancer, etc.	From the day of surgery until the end of the 3rd year after surgery
Secondary	Cognitive function of 3-year survivors	Cognitive function is assessed with the Telephone Interview for Cognitive Status-Modified (TICS-m)	Assessed at the end of the 3rd year after surgery
Secondary	The quality of life in 3-year survivors	The quality of life is assessed with the World Health Organization Quality of Life-BREF (WHOQOL-BREF)	Assessed at the end of the 3rd year after surgery
Secondary	The quality of life in 3-year survivors with chronic pulmonary disease	The quality of life is assessed with the St. George's Respiratory Questionnaire (SGRQ)	Assessed at the end of the 3rd year after surgery