Examining Safety, Efficacy and Feasibility of Preoperative Propranolol in Patients With PDAC.

• Status: Recruiting
• Trial end date: 2035-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The IMPULS trial is a randomized, triple-blinded, placebo controlled, single center, pilot trial examining the efficacy and safety of preoperative propranolol in patients scheduled for pancreatic cancer surgery. The study is conducted as a type 1 hybrid efficacy-implementation trial of 30 patients.

This study is designed to provide pilot data for a future larger perioperative study of propranolol with the aim of improving outcomes for pancreatic cancer surgery.

In total, 30 participants will be allocated in a 1:1 ratio with 15 participants enrolled in each trial arm (propranolol vs. placebo). Participants will be allocated to either 40 mg propranolol twice daily or placebo twice daily in 10 days prior to planned surgery.

Primary outcomes: Evaluating the efficacy of preoperative propranolol on anxiety and in pro-tumorigenic changes (e.g., in the tumor tissue and in blood samples) in patients undergoing surgery for pancreatic cancer. Furthermore, to obtain follow up data (e.g., 90-day mortality, postoperative complications etc. on the patients receiving propranolol versus placebo). Heart rate variability among the participants will also be examined.

Secondary: Examining the safety and tolerability of 40 mg preoperative propranolol twice daily in patients undergoing surgery for pancreatic cancer.

Tertiary: Evaluating the feasibility and implementation of the trial (using the APEASE framework). This will help identify barriers and enablers to a future larger study.

Short-time propranolol treatment is considered safe with a mild and manageable safety-profile. Risk-management, mitigations and guidelines to ensure patient safety is included in the protocol. Since this clinical trial is exploratory in nature, no sample-size calculation is performed.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Zealand University Hospital
• Collaborator: Rigshospitalet, Denmark
• Treatments: Propranolol

Criteria

Inclusion Criteria:

• Patients with suspected surgically resectable pancreatic cancer

• Indication for surgical treatment with curative intend.

• Provide written informed consent.

• Patients minimum 18 years old.

Women of childbearing potential (WOCBP) are defined as women ranging from the period of menarche till the post-menopausal period, unless permanently sterile (e.g., hysterectomy, bilateral salpingectomy and bilateral oophorectomy). Post-menopause is defined as no menses for 12 months without an alternative medical cause.

WOCBP should use a secure and highly effective birth control (as stated in the "Recommendations related to contraception and pregnancy testing in clinical trials", version 1.1., section 4.1, from the Clinical Trials Facilitation and Coordination Group) during the entire period of the trial. In cases of uncertainty regarding pregnancy, additional pregnancy testing either as highly sensitive serum or urine pregnancy test can be used.

Exclusion Criteria:

• Patients with:

• Chronic hypotension, systolic blood pressure < 100 mg Hg for women and < 110 mg Hg for men.

• Bradycardia, pulse < 50 beats per minute.

• Asthma or chronic obstructive lung disease

• Heart insufficiency with affected (< 50 %) left ventricle ejection fraction (LVEF), treated or untreated.

• Kidney insufficiency, defined as eGFR < 20 ml/min.

• Liver insufficiency defined as chronically high liver enzymes or known chronic liver disease (e.g., hepatitis, steatosis, cirrhosis).

• Cor pulmonale

• Cardiogenic shock

• Severe peripheral circulatory disorders

• Known or newly diagnosed current metabolic acidosis (e.g., in recent analysis of arterial puncture).

• Known hypersensitivity to propranolol or to one or more of the excipients.

• Currently untreated pheochromocytoma.

• History of Prinzmetals angina.

• History of sick sinus syndrome or atrioventricular block.

• History of stroke or any previous cardiovascular event.

• History of neoadjuvant oncological treatment for suspected primary pancreatic cancer.

• Recent or present (within 3 months) use of propranolol or any other beta-blocker.

• Recent or present (within 3 months) use of any of the following medications:

anxiolytics, calcium channel blockers, beta-adrenergic receptor agonist.

• Medical history that classifies the patient as frail or unsuitable for inclusion by the examining physician.

• Histopathological examination revealing benign lesion.

• Predictable poor compliance, due to pre-existing psychiatric disease, dementia or not able to read or speak sufficient Danish, resulting in not being able to provide a well-informed written consent.