Clinical trial NCT05727618: The Effect of Pituitrin on the Patients With Pulmonary Hypertension Undergoing Cardiac Surgery
Official title: The Effect of Pituitrin on Postoperative Outcomes in Patients With Pulmonary Hypertension Undergoing Cardiac Surgery: a Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Cardiac Surgery
Hypertension, Pulmonary
Keywords: cardiac surgery
Hypertension, Pulmonary
Pituitary Hormones, Posterior
Extracorporeal Circulation
Lead sponsor: Qianfoshan Hospital
Sponsor class: OTHER
First posted: 2023-02-14
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a parallel group, single blind, randomized controlled trial. Patients with pulmonary hypertension who met the inclusion criteria and planned to undergo elective cardiac surgery under cardiopulmonary bypass from July 1, 2022 to December 1, 2024 in the Department of cardiac surgery of the First Affiliated Hospital of Shandong First Medical University were selected. After removing the aortic blocking forceps, the experimental group immediately injected the test drug (pituitrin 0.04u/ (kg · h)) intravenously, The control group was immediately injected with the corresponding dose of normal saline by intravenous pump. The main outcome was the composite endpoint of all-cause mortality 30 days after operation or common complications after cardiac surgery (stroke, requiring mechanical ventilation for more than 48 hours, deep sternal wound infection, cardiac reoperation, extracorporeal membrane oxygenation, atrial fibrillation or acute renal injury).

Detailed description: Cardiac surgery is the most important treatment for serious coronary heart disease, valvular heart disease, congenital heart disease and other heart diseases. Its postoperative mortality and serious complications have also been widely concerned, especially in patients with pulmonary hypertension. The persistent pulmonary hypertension and systemic vascular paralysis during the perioperative period are the main causes of early postoperative death and serious complications such as organ failure.Catecholamine vasoactive drugs commonly used in cardiac surgery may aggravate the condition of pulmonary hypertension, while the use of drugs to reduce pulmonary hypertension, such as nitric oxide, prostaglandins and phosphodiesterase inhibitors, may worsen the state of systemic vascular paralysis.

Vasopressin and oxytocin are two effective components in pituitrin, and vasopressin is the main component that exerts strong vasoconstrictive effect.Vasopressin binds to receptors distributed in vascular smooth muscle, pituitary and kidney, and exerts its effects by regulating adenosine triphosphate sensitive K+ channel function, nitric oxide production and enhancing vascular response to catecholamine.In addition, oxytocin can also bind to the receptors distributed in the heart and vascular endothelium, and play a role by releasing atrial natriuretic peptide and nitric oxide.Therefore, pituitrin can not only constrict systemic circulation vessels and increase systemic circulation pressure, reduce pulmonary artery pressure and pulmonary vascular resistance, but also protect the heart and kidney.

Therefore, this study intends to explore whether pituitrin has an impact on the prognosis of patients with pulmonary hypertension after cardiac surgery, so as to provide reference for its clinical application.

Eligibility criteria: Inclusion Criteria:

* age ≥18 years and ≤80 years;
* scheduled for elective cardiopulmonary bypass heart surgery (adult congenital heart disease surgery, coronary artery bypass grafting, valve replacement, valvuloplasty, heart transplantation and aortic surgery);
* Patients who had pulmonary hypertension (Mean pulmonary artery pressure at rest ≥ 25mmhg or pulmonary artery systolic pressure (PASP) ≥ 40mmhg as shown by echocardiography);
* sign informed consent.

Exclusion Criteria:

* use pituitrin or vasopressin before operation;
* Patients who had acute coronary syndrome;
* preoperative use of left ventricular assist devices other than intra aortic balloon - pump (IABP);
* Patients who had liver, thyroid and adrenal diseases, severe lung diseases, diabetes;
* Patients who had preoperative renal insufficiency (The increase of serum creatinine (SCR) within 48 h ≥ 0.3mg/dl (or ≥ 26.5 μ mol/L)； Or it is known or speculated that the increase of SCR in the past 7 days is more than 1.5 times of the basic value; Or 0.5ml/kg urine volume per hour for 6H);
* Patients who had severe carotid artery stenosis, preoperative stroke, mental disorder and other difficult to communicate and cooperate;
* Patients who had peripheral vascular disease, allergy to vasopressin or pituitrin, severe hyponatremia (na+ \< 130 mmol/l), acute mesenteric ischemia, pregnancy, malignant tumors, required ECMO and underwent emergency surgery or reoperation;
* Patients who had participated in other clinical studies in recent 3 months.

Primary outcomes:
measure: a composite endpoint of mortality or severe postoperative complications
timeFrame: Within 30 days after cardiac surgery
Secondary outcomes:
measure: incidence of postoperative infection
timeFrame: Within 30 days after cardiac surgery
measure: septic shock
timeFrame: Within 30 days after cardiac surgery
measure: duration of mechanical ventilation
timeFrame: Time from the beginning of mechanical ventilation to the end of mechanical ventilation up to 30 days after cardiac surgery.
measure: postoperative pulmonary complications
timeFrame: Within 30 days after cardiac surgery
measure: time to achieve hemodynamic stability
timeFrame: Within 30 days after cardiac surgery
measure: use of dobutamine or other vasoactive drugs
timeFrame: Within 30 days after cardiac surgery
measure: incidence of digital ischemia
timeFrame: Within 30 days after cardiac surgery
measure: acute mesenteric ischemia
timeFrame: Within 30 days after cardiac surgery
measure: gastrointestinal complications
timeFrame: Within 30 days after cardiac surgery
measure: incidence of acute myocardial infarction
timeFrame: Within 30 days after cardiac surgery
measure: new onset tachyarrhythmia
timeFrame: Within 30 days after cardiac surgery
measure: water poisoning
timeFrame: Within 30 days after cardiac surgery
measure: vasodilative shock
timeFrame: Within 30 days after cardiac surgery
measure: incidence of pulmonary embolism
timeFrame: Within 30 days after cardiac surgery
measure: low cardiac output syndrome
timeFrame: Within 30 days after cardiac surgery
measure: acute respiratory distress syndrome
timeFrame: Within 30 days after cardiac surgery
measure: delirium
timeFrame: Within 30 days after cardiac surgery
measure: need for renal replacement therapy (RRT)
timeFrame: Within 30 days after cardiac surgery
measure: need for hemodialysis
timeFrame: Within 30 days after cardiac surgery
measure: incidence of readmission to ICU
timeFrame: Within 30 days after cardiac surgery
measure: length of ICU stay
timeFrame: Within 30 days after cardiac surgery
measure: length of stay
timeFrame: Within 30 days after cardiac surgery
measure: levels of serum antidiuretic hormone in patients
timeFrame: at entering the operating room(T1), 4 hour(T2), 12 hour(T3) and 24 hour(T4) postoperatively
measure: levels of copeptin in patients
timeFrame: at entering the operating room(T1), 4 hour(T2), 12 hour(T3) and 24 hour(T4) postoperatively
measure: secondary endotracheal intubation
timeFrame: Within 30 days after cardiac surgery
Other outcomes:
Locations:
city: Jinan
country: China
facility: Qianfoshan Hospital, The First Hospital affiliated of Shandong First Medical University
state: Shandong
Study officials:
affiliation: Qianfoshan Hospital, The First Hospital affiliated of Shandong First Medical University
name: Quan Li, doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Qianfoshan Hospital, The First Hospital affiliated of Shandong First Medical University
name: Meng Lv, doctor
role: PRINCIPAL_INVESTIGATOR
References: