Open-Label Placebo Treatment for Acute Postoperative Pain

Study Overview
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Brief Summary
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This study is to evaluate whether the amount of morphine intake in acute postoperative pain following minimally invasive Transforaminal Lumbar Interbody Fusion (TLIF) can be decreased with an Open-Label Placebo (OLP) intervention (comprising the administration of sodium chloride (NaCl) injections and an evidence-based treatment rationale) in comparison to a Treatment As Usual (TAU) control group.

Official Title
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Open-Label Placebo Treatment for Acute Postoperative Pain: A Randomized Controlled Trial (OLP-POP Study)

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: Open-Label Placebo
* Other: treatment as usual


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Scheduled to receive a TLIF procedure at University Hospital Basel (USB) 18 years or older German speaking Able to understand the study and its outcome measures Exclusion Criteria: Known chronic pain, which is unrelated to problem targeted by the surgery Known neuromuscular disease Known mental disorders Known drug or massive alcohol intake or of other psychoactive substances Known kidney or liver disease (glomerular filtration rate (GFR)/ GFR < 30) Contraindications to the class of drugs under investigation, e.g., known hypersensitivity or allergy to the investigational product Parallel participation in another study with investigational drugs More than 30 mg/day (equivalent dose of oral morphine) preoperative opioid consumption

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OLP-Group<br>patients will receive in addition to TAU, 2 open-label Placebo (OLP) injections (containing each 5 ml of NaCl 9%) per day for two consecutive days following minimally invasive TLIF | Drug: Open-Label Placebo<br>* in addition to Treatment as usual, patients receive placebos without concealment (open-label placebo, OLP)<br>|
| Other: TAU-group<br>The treatment as usual (TAU) group will serve as control group and will control for the natural course of postoperative pain under usual medication intake, following minimally invasive TLIF | Other: treatment as usual<br>* usual medication intake following minimally invasive TLIF. TAU consists of 3 gram Paracetamol per os a day, a patient-controlled morphine pump (Maximum of 2 milligram (mg) every 12 minutes) and rescue medication (1000 mg of Metamizol, maximum every 6 hours)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in morphine consumption | cumulative dose (i.e., total amount) of self-administered morphine within 48 hours starting on the first day post-surgery at 09:00 am (T1) and ending on the third day of surgery at 09:00 am (T5) | starting on the first day post-surgery at 09:00 am (T1) and ending on the third day of surgery at 09:00 am (T5). morphine records will be read out twice a day (9:00 am and 16:45) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in morphine request rates | Morphine demand behaviour will be measured by the total number of successful and unsuccessful clicks on the Patient Controlled Analgesia (PCA) pump between T1 and T5 (48 hours) | between T1 (9:00 am day post surgery) and T5 (9:00 am, 3rd day post surgery) (48 hours, morphine records will be read out twice a day (9:00 am and 16:45) | 
| Difference in pain intensity at rest | back and leg pain intensity at rest will be measured separately by two 11-point Numeric Rating Scales (NRS, i.e., back / leg pain intensity at rest), which assesses pain intensity by asking participants to rate their pain intensity on a 0 to 10 scale, where 0 is no pain and 10 is worst pain possible | The two at rest scales (for leg and back pain) will be administered every two hours starting after transport to normal ward on the day of surgery (T0) until 09:00 am on the third day post-surgery (T5) and as well before surgery (T-1) | 
| Difference in pain intensity while walking | back and leg pain intensity while walking will be measured separately by two 11-point Numeric Rating Scales (i.e., back / leg pain intensity while walking), which assesses pain intensity by asking participants to rate their pain intensity on a 0 to 10 scale, where 0 is no pain and 10 is worst pain possible | The two while walking scales will be administered the day before surgery (T-1), after transport to normal ward (i.e., at T0), at T2 (16:45, 1st day after surgery), T4 (16:45 2nd day post surgery), respectively. | 
| Difference in comprehensive pain assessment and patients' perception of postoperative pain management | will be assessed by the German version of the International Pain Outcomes (IPO) Questionnaire. The IPO assesses patients pain experience and outcomes regarding patient reported aspects | The scale will be administered on the day before surgery (T-1), in the morning of the first day post-surgery (i.e., between 07:00 and 09:00; T0) , after the pain nurse visit 09:00 am day 2 (T3) and 09:00 am day 3 (T5) post-surgery | 
| Difference in requested rescue analgesics | will be regularly assessed as part of standard procedures of the hospital and will be documented in the electronic hospital record of each patient | After trial completion of participants, study team members will extract the data from hospital records for the time periods of: the day of surgery (T0) till first day post-surgery at 09:00 am (T1) and T1 to T5 (09:00 am day 3 post-surgery) | 
| Opioid-Related Side Effects | nausea, vomiting and constipation (i.e., stool frequency, vomiting and amount of delivered laxatives and antiemetics) are regularly assessed and documented as part of standard hospital procedures | After trial completion of participants, study team members will extract the data from hospital records for the time periods of: the day of surgery (T0) till first day post-surgery at 09:00 am (T1) and T1 to T5 (09:00 am day 3 post-surgery) | 
| Length of Post-Surgery Hospitalisation | Length of Post-Surgery Hospitalisation, upon participants trial completion this data will be extracted by study team members from the electronic hospital record of each patient | Length of Post-Surgery Hospitalisation, approximately 14 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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postoperative pain, Open-Label Placebo, morphine, Transforaminal Lumbar Interbody Fusion