Vasopressin versus norepinephrine for immediate postoperative mean pulmonary arterial pressure reduction after pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension: randomized trial

The primary objective is to compare the efficacy of vasopressin versus norepinephrine in achieving immediate postoperative reduction in mean pulmonary arterial pressure after pulmonary endarterectomy, which is clinically relevant for early hemodynamic stabilization in chronic thromboembolic pulmonary hypertension. The secondary objectives are to compare changes over time in mean pulmonary arterial pressure, pulmonary vascular resistance, cardiac output, and pulmonary artery compliance at CPB weaning, ICU admission, and Swan-Ganz catheter removal; the incidence of CPB weaning failure; postoperative acute kidney injury or the need for renal replacement therapy; supraventricular arrhythmia; airway hemorrhage requiring therapeutic intervention; major pulmonary complications; major cardiac complications; major gastrointestinal complications; major neurological complications; surgical site infection; surgical reintervention; ICU and hospital length of stay; and 30-day all-cause mortality.

The sponsor did not provide the total number of participants. The trial population included patients of both sexes and adults aged 18 years or older. Participants were scheduled for pulmonary endarterectomy surgery and had chronic thromboembolic pulmonary hypertension. Selection was based on eligibility for the surgery and the ability to provide written informed consent. In women of childbearing potential, a negative serum pregnancy test and adequate contraception were required. Affiliation to the French social care service was also specified. No information was provided on general health status beyond the condition studied, and no relevant lifestyle considerations were reported.

This is a randomized, open-label, controlled phase III trial comparing vasopressin with norepinephrine for the immediate post-operative reduction in mean pulmonary arterial pressure after pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension. Eligible adults scheduled for surgery are screened for inclusion criteria, including informed consent and, where applicable, a negative pregnancy test with adequate contraception. After enrollment, participants are assigned to one of the two intravenous infusion treatment groups and are followed during the perioperative and post-operative hospital period. Study assessments are performed at the screening visit, during the operative and immediate post-operative period for efficacy and safety measurements, and at the end-of-study visit, which occurs after completion of the hospital follow-up and collection of all outcome data. The expected participant involvement extends from screening before surgery through hospital discharge and completion of the study assessments. Early termination may occur if inclusion criteria are no longer met, if consent is withdrawn, or if discontinuation is required for safety, clinical deterioration, or other investigator-determined reasons.

The investigational treatment was argipressin, administered as Reverpleg 40 U.I./2 ml solution for infusion. It was given by intravenous infusion at a total dose of 47.52 IU. The study compared this treatment with the comparator norepinephrine, administered as NORADRENALINE VIATRIS 2 mg/ml SANS SULFITES, solution for infusion. The comparator was given by intravenous infusion at a total dose of 240 mg. Both treatments were used in a randomized open-label clinical trial evaluating the immediate post-operative reduction in mean pulmonary arterial pressure following pulmonary endarterectomy surgery. No additional information on dosing schedule, administration details, or compliance monitoring was provided.

Efficacy will be assessed by comparing mean pulmonary arterial pressure (mPAP) between vasopressin and norepinephrine. The primary endpoint is mPAP in millimeter of mercury (mmHg) measured by the Swan-Ganz catheter in the operating room, recorded at the end of skin closure immediately after completion of the pulmonary endarterectomy procedure.

Secondary efficacy assessments include mPAP, vascular pulmonary resistance in wood unit, cardiac output in liter per minute, and pulmonary artery compliance, all measured by the Swan-Ganz catheter.