E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
postoperative secondary mechanical hyperalgesia and postoperative pain |
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E.1.1.1 | Medical condition in easily understood language |
Postoperative pain amplification at the incisional site and postoperative pain |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The goal of the present study is to prove that a two-day (48h) preoperative capsaicin skin treatment with capsaicin 8% patch leading to desensitization of capsaicin-sensitive (i.e. TRPV1-positive) fibers at the site of incision reduces postoperative mechanical secondary hyperalgesia on postoperative day (POD) one, in routine surgical patients. |
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E.2.2 | Secondary objectives of the trial |
Further goals of this study are to provide pilot data on the following hypotheses (i) TRPV1-fiber desensitization leads to a reduction of acute postoperative pain and/or analgesic consumption; (ii) the area of secondary hyperalgesia around the incisional site is reduced in patients pretreated with capsaicin; (iii) TRPV1-fiber desensitization leads to reduced primary hyperalgesia measured by electrical stimulation; (iv) postoperative pain amplification mechanisms (i.e. LTP-like pain plasticity via TRPV1-positive fibers) are a major factor in the development of persistent postsurgical pain; (v) TRPV1-expressing fibers are responsible for hyperalgesia in surgical patients as well thereby demonstrating translationability of preclinical results; (vi) a two-day capsaicin treatment immediately reduces C-fiber density at the site of patch application.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• male or female, at least 18 years of age • planned elective surgery requiring incision of the abdominal wall • currently pain free or suffering from spontaneous pain in the last 24 hours of less than 4 on the numeric rating scale in the area of planned surgery • able to understand, read, and write German • willing and able to give informed consent
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E.4 | Principal exclusion criteria |
• patients undergoing scheduled surgery with less than 3 full days until surgery date • patients undergoing surgery with planned local anesthetic procedures (peripheral nerve block, , epidural or spinal anesthesia) or planned use of NMDA-receptor antagonists (i.e. ketamine i.v. or p.o.) • patients scheduled for postoperative controlled respiratory treatment at the intensive care unit (ICU) • patients under the age of 18 • patients suffering from acute or chronic pain with an intensity of greater than 3 on the numeric rating scale (spontaneous within the last 24 hours) • patients currently on prescribed regular analgesic medication • patients suffering from any known psychiatric condition • patients suffering from unstable hypertension • patients with implanted cardiac converter or pacemaker • pregnancy or breast-feeding • known abuse of alcoholic beverages or any illegal drug • known allergy against interventional or placebo medication, patch contents or study assessment devices • unable or unwilling to give informed consent • unable or unwilling to follow investigator’s instructions • unable or unwilling to comply with study protocol • patients suffering from any known medical conditions which may interact with study medication, study objectives, or compliance of subject with study tasks
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome parameter is mean pain intensity to 7 defined pinprick stimuli applied in the area of secondary mechanical hyperalgesia surrounding the wound incision in capsaicin treated or vehicle treated (placebo) site on postoperative day one, i.e. 24 (±4) hours after surgery. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
postoperative day one, i.e. 24 (±4) hours after surgery. |
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E.5.2 | Secondary end point(s) |
• Mean pain ratings* (pain at the moment (at rest and upon movement), average pain since the day before, most intense pain since the day before) on postoperative day (POD) one, POD two, POD three. • Mean pain ratings and highest pain rating recorded during the first 90 minutes at the post-anesthesia care unit and pain rating upon discharge from the post-anesthesia care unit. • Daily consumption of opioids (i.e. analgesic consumption) administered via patient-controlled analgesia on POD 1, POD 2, and POD 3. • Mean pain to pinprick stimulus in the area of secondary mechanical hyperalgesia around incision site on POD three. • Mean pain ratings to electrical stimulation at the site of incision on POD 1 and POD 3 after the operation. • The mean area of secondary hyperalgesia around the site of incision on POD 1 and POD 3. • The mean pressure pain thresholds at the remote site (proximal tibia) on POD 1 and POD 3. • Conditioned pain modulation profile, measured by increase of pressure pain thresholds after cold pressor test versus baseline, and its impact on acute and persistent postoperative pain. • Incidence of persistent postoperative pain (NRS >0) at three months in both groups. *Pain ratings = pain rated on the numeric rating scale ranging from 0 to 100 (0 indicating no pain and 100 indicating most intense pain imaginable.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
postoperative day one, day two, and day three postoperative month 3 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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upon follow-up at postoperative month 3 |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |