Plans for assessment and collection of outcomes

Data will be collected by trained registered nurses (RNs) from the ward to ensure accuracy and completeness. Any missing data is expected to occur randomly due to the training and standardized procedures in place. Statistical analysis will be performed only on data from patients who have received the investigational medication; data from patients who did not receive the investigational medication will be excluded. The primary and secondary outcomes (detailed below) will be recorded on standardized charts. These charts will be entered into our REDCap database. Three months after surgery, patients will be contacted by the investigator for a follow-up phone call to complete the final chart and the EQ-5D-5L questionnaire.

Primary outcome Daily consumption of opioids

Postoperative opioid consumption will be measured as the mean daily consumption of rescue and long-acting morphine equivalents within the first 72 h after surgery. The morphine equivalent dose for various opioids will be calculated. The source of this data is the medical chart, with RNs recording the amounts on the observation chart, which is subsequently entered into REDCap.

Secondary outcomes Postoperative pain assessment

Patients will assess pain intensity in the hip at rest and during mobilization using the Verbal Rating Scale (VRS). Pain intensity will be assessed once daily for the first three postoperative days. This data will be sourced from the observation chart.

Time to standing up

The number of hours until the patient first stands postoperatively will be recorded. This data will be sourced from the electronic patient record, which logs timestamps such as time from knife-to-skin and return to the ward.

Cumulated Ambulation Score (CAS)

Physiotherapists routinely use the CAS to assess patient mobility. This score will be recorded once daily for the first three postoperative days on the observation chart.

Postoperative Nausea or Vomiting (PONV)

The occurrence of PONV will be recorded as “yes” or “no” once daily for the first three postoperative days on the observation chart by the RNs.

Time to discharge

The number of days from arrival at the ward until the patient is deemed ready for discharge will be recorded. This decision is made by the orthopedic doctor during ward rounds. If a patient is transferred to another department, they are still considered hospitalized, and data collection stops. This data will be sourced from timestamps in the electronic patient record and entered into REDCap.

Need for an antidote

The administration of an antidote during admission will be recorded as “yes” or “no” once daily for the first three postoperative days on the observation chart. The source of this data is the medical chart.

Confusion Assessment Method (CAM)

Patients will be monitored for signs of delirium using the CAM for the first 3 days after surgery. The method records 0 for no signs of delirium and 1 for delirium. Data will be sourced from the electronic patient record and recorded on the observation chart.

Constipation

The occurrence of constipation during admission will be recorded on the observation chart by the RNs.

Three-month follow-up Continued opioid consumption

Continued opioid consumption will be recorded directly into REDCap as the mean daily consumption of both long-acting opioids and rescue medication, based on the medication chart and patient report. Various opioids will be converted into daily morphine milligram equivalents.

Pain

Patients will assess their pain level using the VRS at rest and during mobilization on the follow-up day. Data will be entered directly into REDCap.

EQ-5D-5L

The investigator will complete this validated generic questionnaire with the patient. The EQ-5D-5L, previously used in studies with hip fracture patients [21], can be completed directly in REDCap using the patient’s responses.

Mobility

Patients’ mobility will be assessed using the New Mobility Score, as utilized in other studies [22]. The score will be calculated directly in REDCap based on patient statements.

Persistent side-effects

The presence of persistent adverse reactions, including dizziness, vertigo, nausea, vomiting, constipation, and drowsiness, will be recorded based on patient statements and entered directly into REDCap

Plans to promote participant retention and complete follow-up

RNs at the ward manage data collection. This way the participant does not have any trial-specific activities and can focus on their rehabilitation. Furthermore, we administer the study drug in the context of surgery and only this one time. Consequently, we expect full participant retention as participation involves no inconvenience.

Seeing that the expected mean age of the participants is 80–82 years old, we refrain from any electronic follow-up questionnaires. Instead, we rely on a phone call, which should be familiar to the participants. This is also a lot less inconvenient than a follow-up visit at the hospital. We collect no data from participants who discontinue intervention protocols. However, we register any serious adverse reaction for 12 days after study drug administration for all patients. This is in accordance with Good Clinical Practice (GCP) where serious adverse reactions need to be registered for five half-lives.

Data management

The principal investigator will conduct a list of all patients screened for inclusion. The list will cover both included and excluded patients and include patient number, CPR number, and initials. Furthermore, an identification list will be conveyed by the principal investigator listing all included patients with patients’ full name, CPR number, and patient study number. Both lists will be stored in a locked office within a locked cabin. The principal investigator ensures direct access to any data, documents, or journals in case of monitoring, audits, or inspections from the GCP units and The Danish Medicine Agency. We use double data entry where trained RNs fill out a standardized observation chart. The study investigator later enters these data into our secure REDCap database and double checks data values.

For every included patient, an eCRF will be completed. Any editing will be logged so that original data can be retrieved at any time. The log will also show the time any data has been edited and by whom. Demographic data regarding each patient is retrieved from the journal and registered in the eCRF. This includes age, gender, co-morbidities, diagnosis (fracture type), height, weight, medicine consumption, drug addiction, smoking status, and the type of anesthesia used.

Confidentiality

Any person-sensitive data processed in the study is managed according to the General Data Protection Regulation, the Danish Data Protection Act, and the Danish Health Act. Any information kept on paper will be stored in a locked cabin within a locked office. Any electronic data is stored in REDCap, where access is limited to specified users.

Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in this trial/future use

We do not use any biological specimens in this trial.