Prophylactic Penehyclidine Hydrochloride Inhalation and 3-year Outcome After Surgery
19 апреля 2022 г. обновлено: 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.
Обзор исследования
Статус
Завершенный
Вмешательство/лечение
Подробное описание
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.
Тип исследования
Интервенционный
Регистрация (Действительный)
864
Фаза
- Фаза 4
Контакты и местонахождение
В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.
Места учебы
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Beijing
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Beijing, Beijing, Китай, 100034
- Peking University First Hospital
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Критерии участия
Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.
Критерии приемлемости
Возраст, подходящий для обучения
50 лет и старше (Взрослый, Пожилой взрослый)
Принимает здоровых добровольцев
Нет
Полы, имеющие право на обучение
Все
Описание
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.
Учебный план
В этом разделе представлена подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.
Как устроено исследование?
Детали дизайна
- Основная цель: Профилактика
- Распределение: Рандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Четырехместный
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
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Экспериментальный: 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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Плацебо Компаратор: 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.
|
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.
|
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Duration of overall survival within 3 years after surgery
Временное ограничение: 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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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Survival rates at different timepoints after surgery
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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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Соавторы и исследователи
Здесь вы найдете людей и организации, участвующие в этом исследовании.
Спонсор
Публикации и полезные ссылки
Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.
Общие публикации
- 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.
- 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.
- 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.
- Lawrence VA, Hilsenbeck SG, Mulrow CD, Dhanda R, Sapp J, Page CP. Incidence and hospital stay for cardiac and pulmonary complications after abdominal surgery. J Gen Intern Med. 1995 Dec;10(12):671-8. doi: 10.1007/BF02602761.
- Khan NA, Quan H, Bugar JM, Lemaire JB, Brant R, Ghali WA. Association of postoperative complications with hospital costs and length of stay in a tertiary care center. J Gen Intern Med. 2006 Feb;21(2):177-80. doi: 10.1111/j.1525-1497.2006.00319.x.
- Kor DJ, Warner DO, Alsara A, Fernandez-Perez ER, Malinchoc M, Kashyap R, Li G, Gajic O. Derivation and diagnostic accuracy of the surgical lung injury prediction model. Anesthesiology. 2011 Jul;115(1):117-28. doi: 10.1097/ALN.0b013e31821b5839.
- 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.
- Smith PR, Baig MA, Brito V, Bader F, Bergman MI, Alfonso A. Postoperative pulmonary complications after laparotomy. Respiration. 2010;80(4):269-74. doi: 10.1159/000253881. Epub 2009 Oct 28.
- Thomsen T, Villebro N, Moller AM. Interventions for preoperative smoking cessation. Cochrane Database Syst Rev. 2014 Mar 27;2014(3):CD002294. doi: 10.1002/14651858.CD002294.pub4.
- 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.
- Hulzebos EH, Smit Y, Helders PP, van Meeteren NL. Preoperative physical therapy for elective cardiac surgery patients. Cochrane Database Syst Rev. 2012 Nov 14;11(11):CD010118. doi: 10.1002/14651858.CD010118.pub2.
- 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.
- 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.
Даты записи исследования
Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.
Изучение основных дат
Начало исследования (Действительный)
10 ноября 2018 г.
Первичное завершение (Действительный)
1 декабря 2021 г.
Завершение исследования (Действительный)
1 декабря 2021 г.
Даты регистрации исследования
Первый отправленный
3 марта 2019 г.
Впервые представлено, что соответствует критериям контроля качества
7 марта 2019 г.
Первый опубликованный (Действительный)
11 марта 2019 г.
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
20 апреля 2022 г.
Последнее отправленное обновление, отвечающее критериям контроля качества
19 апреля 2022 г.
Последняя проверка
1 апреля 2022 г.
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- 2018[213]
Планирование данных отдельных участников (IPD)
Планируете делиться данными об отдельных участниках (IPD)?
Нет
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Нет
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
Нет
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .