Examining the impact of propranolol on preoperative anxiety and on tumorigenic changes in patients with pancreatic ductal adenocarcinomas: a randomized, triple-blinded, placebo-controlled pilot trial (The IMPULS trial)
- Conditions
- Pancreatic ductal adenocarcinoma (PDAC)
- Registration Number
- 2023-506553-37-00
- Lead Sponsor
- Zealand University Hospital
- Brief Summary
The study will be conducted as a pilot study to test efficacy, safety and feasibility of propranolol on preoperative anxiety in patients undergoing abdominal surgery for suspected pancreatic cancer. Furthermore, we will explore the implementation of the trial including compliance of the participants in a hybrid type 1 setup. A total of 30 participants will be included and randomized to receive either propranolol or placebo twice daily with 15 patients in each arm. Following this study, a power calculation will be done to reveal the actual number of needed participants in each arm for a potential follow-up randomized clinical trial on primary outcomes of interest. Thus, the results from this study can be used for future power calculations for clinical trials related to this topic.
Primary objectives: Efficacy
Evaluating the efficacy of preoperative propranolol on patient-experienced anxiety and on tumorigenic gene expression compared to placebo is the primary objective of this trial.
We further divide the primary objectives in to primary clinical objectives, primary translational objectives and exploratory endpoints.
Primary clinical objectives
The primary clinical objectives are to evaluate preoperative patient-experienced anxiety in patients receiving the nonselective 2-adrenergic receptor inhibitor, propranolol, compared to placebo.
Further, we will measure heart rate variability (HRV) in order to evaluate changes in the autonomous nervous system in relation to surgery. HRV is calculated from the interval variation between consecutive R waves in an ECG time series69,70, and results suggest that it is associated with the intra- and postoperative complications71. As HRV reflects sinoatrial node regulation, we expect it to be affected by the beta-adrenergic blockade caused by preoperative propranolol. Analyzing this relation will provide essential knowledge in understanding how HRV behaves perioperatively.
Lastly, we will make a follow up on the participants receiving propranolol compared to placebo.
Primary translational objectives:
The primary translational objectives are to examine the systemic (biochemical) and local changes (TME of resections) to propranolol treatment compared to placebo. Alterations in pro-metastatic and proinflammatory genes will specifically be analyzed.
Secondary objective: Safety
The secondary objective is to assess tolerance and safety of the intervention in this pilot study (e.g., adverse effects, number of patients that need dose reduction etc.). We will evaluate changes in heart rate (HR) and blood pressure (BP) during the intervention period to test safety and tolerability of preoperative propranolol.
2.3.3 Tertiary objectives: Feasibility
Additionally, we will examine the feasibility of this intervention using the APEASE framework72, which assesses factors like affordability, practicability, effectiveness, acceptability, side-effects, and equity, thereby determining the willingness to adopt this strategy. This will help identify barriers and enablers to a future larger study. The details regarding the APEASE framework are described under assessments.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 30
Patients with suspected surgically resectable pancreatic cancer. Indication for surgical treatment with curative intend. Patients minimum 18 years old. Patients who can provide written informed consent.
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). Currently untreated pheochromocytoma. History of Prinzmetals angina. History of sick sinus syndrome or atrioventricular block. History of neoadjuvant oncological treatment for suspected primary pancreatic cancer. Recent or present (within 1 months) use of propranolol or any other beta-blocker. Recent or present (within 1 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.
Study & Design
- Study Type
- Not specified
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Anxiety levels measured by The Hamilton Anxiety Rating Scale (HAM-A) and by The Hospital Anxiety and Depression Scale (HADS). The European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QoL) for pancreatic cancer will be used to assess quality of life. HRV data calculated from continuous ECG gathered by a Holter monitor. Follow up data: postoperative complications, survival 30-, 90- days and 1, 3-, 5- years after surgery. Blood and tissue sampling Anxiety levels measured by The Hamilton Anxiety Rating Scale (HAM-A) and by The Hospital Anxiety and Depression Scale (HADS). The European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QoL) for pancreatic cancer will be used to assess quality of life. HRV data calculated from continuous ECG gathered by a Holter monitor. Follow up data: postoperative complications, survival 30-, 90- days and 1, 3-, 5- years after surgery. Blood and tissue sampling
- Secondary Outcome Measures
Name Time Method Safety: Changes in resting HR and BP during the intervention. Symptoms and side effects to medicine: light-headedness, lethargy, hypotension, bradycardia and other symptoms/side-effects. Tertiary end points: feasibility and implementation using the APEASE framework Safety: Changes in resting HR and BP during the intervention. Symptoms and side effects to medicine: light-headedness, lethargy, hypotension, bradycardia and other symptoms/side-effects. Tertiary end points: feasibility and implementation using the APEASE framework
Trial Locations
- Locations (2)
Zealand University Hospital
🇩🇰Koege, Denmark
Rigshospitalet
🇩🇰Copenhagen Oe, Denmark
Zealand University Hospital🇩🇰Koege, DenmarkIsmail GögenurSite contact+4526336426igo@regionsjaelland.dk