None listed
Conditions
Brief summary
Patients often experience low blood pressure following major surgery, which may be an emergency situation that could compromise organ function and lead to complications and even death. The trial is a pilot trial of tablet-based therapies that increase the blood pressure and see if they would be useful to prevent low blood pressure after surgery in preparation for a large definitive study in the future. The pilot trial will examine how many patients can be enrolled, as well as how acceptable the trial is to patients, clinicians and researchers, whether there are any problems in the design or execution of the trial and whether the consent procedures which have had to be specially designed for the complex situation after surgery are acceptable. The two medications being tested are widely used in clinical practice to treat low blood pressure that occurs when part of the nervous system does not regulate blood pressure properly called orthostatic hypotension, which the researchers believe there is a mechanism linking this problem to low blood pressure after surgery. Any treatment that could prevent this complication of surgery while being simpler than current options like admission to intensive care would be an important development. This pilot trial will establish the groundwork for a definitive clinical trial in the future that would aim to help reduce the risk of complications and promote recovery after surgery while using health resources efficiently.
Interventions
The trial involves two intervention groups:
1. Midodrine 10mg oral tablet (as encapsulated GMP-certified product) every eight hours over the first 24 hours post-operatively, the first dose being administered within 4 hours of surgery.
2. Atomoxetine 18mg oral tablet (as encapsulated GMP-certified product) once, followed by placebo partially pregelatinized starch filled capsules at 8 and 16 hours after the first administration of investigational product, the first dose being administered within
The trial involves two intervention groups: 1. Midodrine 10mg oral tablet (as encapsulated GMP-certified product) every eight hours over the first 24 hours post-operatively, the first dose being administered within 4 hours of surgery. 2. Atomoxetine 18mg oral tablet (as encapsulated GMP-certified product) once, followed by placebo partially pregelatinized starch filled capsules at 8 and 16 hours after the first administration of investigational product, the first dose being administered within 4 hours of surgery.. Adherence to the allocated intervention will be checked via the electronic medical record.
Sponsors
The Royal Melbourne Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The study will include patients: • aged equal to or greater than 18 years, and • who have had major non-cardiac, non-obstetric surgery, under general anaesthesia who are expected to stay at least two postoperative nights in hospital, and • who are hypotensive (SBP <90 mmHg) for at least 10 minutes in the PACU or who are administered vasoactive medication in PACU, • who are assessed as suitable for discharge to the ward, and • who are able to communicate in English, including with the support of an interpreter.
Exclusion criteria
The study will exclude potential participants where: • age is less than 18 years old • hypotension was present before surgery • there is a clear cause of hypotension not related to vasodilation as assessed by the treating anaesthetist, including: o arrhythmia o bleeding requiring intervention o acute reduction in cardiac output o anaphylaxis o other clinical explanation requiring specified treatment • the patient is in cardiac arrest, • they are receiving intravenous vasopressor infusions and are planned for admission to the intensive care unit, • they are unable to safely swallow capsules, • there is a surgical necessity to avoid vasopressors o Intracranial neurosurgery o Renal transplant o Bowel anastomosis o Reconstructive flap surgery (inc. DIEP, limb or head and neck free flap) • they are receiving dialysis, • they are pregnant or breastfeeding, • they are unable to communicate at all in English, • There is a known contraindication to a study medication: o Hypersensitivity to the active substance or to any of the excipients o Hypersensitivity to atomoxetine or any excipients in this product. o Severe organic heart disease (e.g., bradycardia, recent heart attack, congestive heart failure, cardiac conduction disturbances or aortic aneurysm). o Hypertension (current and severe – e.g., SBP > 160 mmHg) o Serious obliterative blood vessel disease, cerebrovascular occlusions and vessel spasms. o Acute kidney disease or severe renal impairment (creatinine clearance of less than 30 ml/min). o Serious prostate disorder o Urinary retention o Proliferative diabetic retinopathy o Phaeochromocytoma. o Hyperthyroidism or thyrotoxicosis. o Narrow angle glaucoma. o Uncontrolled hyperthyroidism o Use of Monoamine Oxidase Inhibitors with other drugs that affect brain monoamine concentrations • Are previously enrolled in the FAME study • Or are prescribed medications that inhibit cytochrome CYP2D6
Outcome results
None listed