Prophylactic Penehyclidine Hydrochloride Inhalation and 3-year Outcome After Surgery
2022年4月19日 更新者：Dong-Xin Wang、Peking University First Hospital
Impact of Prophylactic Penehyclidine Hydrochloride Inhalation on Long-term Outcome in High-risk Patients: 3-year Follow-up of a Randomized Controlled Trial
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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (実際)
864
段階
- フェーズ 4
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Beijing
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Beijing、Beijing、中国、100034
- Peking University First Hospital
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
50年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- Age of 50 years or over;
- Scheduled to undergo open or laparoscope assisted upper abdominal or intrathoracic surgery;
- The expected duration of surgery is 2 hours or longer;
- Identified at high risk of PPCs according to the ARISCAT risk score (ARISCAT predictive score ≥45).
Exclusion Criteria:
- American Society of Anesthesiologists (ASA) physical classification ≥ IV or the expected survival duration ≤ 24 h;
- Preoperative history of prostatic hypertrophy or glaucoma;
- History of myocardial infarction, severe heart dysfunction (New York Heart Association functional classification ≥ 3) or tachyarrhythmia within one year;
- Inhalation of β2-receptor activator, M-receptor blockers and/or glucocorticoids within one month before surgery;
- Severe renal dysfunction (requirement of renal replacement therapy) or severe hepatic dysfunction (Child-Pugh grade C);
- History of acute stroke within three months before surgery;
- Refuse to participate in the study or unable to cooperate with the inhalation therapy;
- 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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：防止
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：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.
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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
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プラセボコンパレーター：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.
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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.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Duration of overall survival within 3 years after surgery
時間枠：From the day of surgery until the end of the 3rd year after surgery
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Duration of overall survival within 3 years after surgery
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From the day of surgery until the end of the 3rd year after surgery
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Survival rates at different timepoints after surgery
時間枠：At the end of the 1st, 2nd, and 3rd year after surgery
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Survival rates at different timepoints after surgery
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At the end of the 1st, 2nd, and 3rd year after surgery
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Duration of recurrence-free survival within 3 years after surgery
時間枠：From the day of surgery until the end of the 3rd year after surgery
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Duration of recurrence-free survival within 3 years after surgery for primary cancer
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From the day of surgery until the end of the 3rd year after surgery
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Ocurrence of new-onset diseases during the 3-year period after surgery
時間枠：From the day of surgery until the end of the 3rd year after surgery
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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.
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From the day of surgery until the end of the 3rd year after surgery
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Cognitive function of 3-year survivors
時間枠：Assessed at the end of the 3rd year after surgery
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Cognitive function is assessed with the Telephone Interview for Cognitive Status-Modified (TICS-m)
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Assessed at the end of the 3rd year after surgery
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The quality of life in 3-year survivors
時間枠：Assessed at the end of the 3rd year after surgery
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The quality of life is assessed with the World Health Organization Quality of Life-BREF (WHOQOL-BREF)
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Assessed at the end of the 3rd year after surgery
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The quality of life in 3-year survivors with chronic pulmonary disease
時間枠：Assessed at the end of the 3rd year after surgery
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The quality of life is assessed with the St. George's Respiratory Questionnaire (SGRQ)
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Assessed at the end of the 3rd year after surgery
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Sabate 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.
- Khuri SF, Henderson WG, DePalma RG, Mosca C, Healey NA, Kumbhani DJ; Participants in the VA National Surgical Quality Improvement Program. Determinants of long-term survival after major surgery and the adverse effect of postoperative complications. Ann Surg. 2005 Sep;242(3):326-41; discussion 341-3. doi: 10.1097/01.sla.0000179621.33268.83.
- Fisher BW, Majumdar SR, McAlister FA. Predicting pulmonary complications after nonthoracic surgery: a systematic review of blinded studies. Am J Med. 2002 Feb 15;112(3):219-25. doi: 10.1016/s0002-9343(01)01082-8.
- Canet J, Gallart L, Gomar C, Paluzie G, Valles J, Castillo J, Sabate 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.
- Wu CL, Hurley RW, Anderson GF, Herbert R, Rowlingson AJ, Fleisher LA. Effect of postoperative epidural analgesia on morbidity and mortality following surgery in medicare patients. Reg Anesth Pain Med. 2004 Nov-Dec;29(6):525-33; discussion 515-9. doi: 10.1016/j.rapm.2004.07.002.
- Matot I, Oppenheim-Eden A, Ratrot R, Baranova J, Davidson E, Eylon S, Peyser A, Liebergall M. Preoperative cardiac events in elderly patients with hip fracture randomized to epidural or conventional analgesia. Anesthesiology. 2003 Jan;98(1):156-63. doi: 10.1097/00000542-200301000-00025.
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- Antoniou SA, Antoniou GA, Koch OO, Kohler G, Pointner R, Granderath FA. Laparoscopic versus open obesity surgery: a meta-analysis of pulmonary complications. Dig Surg. 2015;32(2):98-107. doi: 10.1159/000371749. Epub 2015 Mar 3.
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- 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.
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- Kroenke K, Lawrence VA, Theroux JF, Tuley MR. Operative risk in patients with severe obstructive pulmonary disease. Arch Intern Med. 1992 May;152(5):967-71.
- Celli BR. Perioperative respiratory care of the patient undergoing upper abdominal surgery. Clin Chest Med. 1993 Jun;14(2):253-61.
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研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2018年11月10日
一次修了 (実際)
2021年12月1日
研究の完了 (実際)
2021年12月1日
試験登録日
最初に提出
2019年3月3日
QC基準を満たした最初の提出物
2019年3月7日
最初の投稿 (実際)
2019年3月11日
学習記録の更新
投稿された最後の更新 (実際)
2022年4月20日
QC基準を満たした最後の更新が送信されました
2022年4月19日
最終確認日
2022年4月1日
詳しくは
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