E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Introduction of collagenase clostridium histolyticum injection for the treatment of Dupuytren’s contractures. |
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E.1.1.1 | Medical condition in easily understood language |
Dupuytren’s contracture is a hand deformity in which knots of tissue under the skin create a thick cord that can pull the fingers (usually the ring and pinky fingers) into a bent position. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10013873 |
E.1.2 | Term | Dupuytren's contracture operation |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 introduction of collagenase clostridium histolyticum (commercialized as Xiapex® or Xiaflex®) injection has been an advance in the treatment of Dupuytren’s contractures. The treatment consists of two phases. In the first phase, the collagenase is injected into the Dupuytren’s cord. In a second phase, 24 to 48 hours later, manipulation of the injected fingers is planed. Passive finger extension ruptures the enzymatically weakened Dupuytren’s cord. The anesthetic challenges for this procedure are finding one anesthetic intervention for both injection of collagenase and manipulation of the cords are painful. With the upcoming availability of liposomal bupivacaine (Exparel®), we hypothesize that anesthesia and analgesia for both procedures can be accomplished with a single anesthetic intervention by blocking both median and ulnar nerve. |
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E.2.2 | Secondary objectives of the trial |
* Numeric rating scale (NRS) * Overall Benefit of Analgesia Score (OBAS) (Lehmann, 2010) * Start and duration of the sensorial block with monitoring of the second phase of the sensorial block * Start and duration of the sensorial block with monitoring of the second phase of the sensorial block motor block * Duration of sleep and sleepquality during the week of intervention * Patient satisfaction concerning analgesia * Functionality of the operated limb * Patient satisfaction * Surgeon satisfaction |
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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 at screening • Scheduled to undergo Dupuytren’s contracture release • American Society of Anesthesiologists (ASA) physical status I, II or III • Able to demonstrate sensory function by exhibiting sensitivity to cold, pinprick and light touch • Female subjects must be surgically sterile or have a monogamous partner who is surgically sterile; or at least 2 years postmenopausal or practicing double-barrier contraception; or practicing abstinence (must agree to use double-barrier contraception in the event of sexual activity); or using an insertable, injectable, transdermal, or combination oral contraceptive approved by the FDA for greater than 2 months prior to screening and commit to the use of an acceptable form of birth control for the duration of the study and for 30 days after completion of the study • Able to understand the English or Dutch language, purpose and risks of the study. • Able to provide informed consent and authorization to use protected health information, adhere to the study visit schedule and complete all study assessments |
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E.4 | Principal exclusion criteria |
• Currently pregnant, nursing or planning to become pregnant during the study or within 1 moth after study drug administration • Planned concurrent surgical procedure • Previous Dupuytren’s contracture on the hand being considered for surgery • History of hypersensitivity to local anesthetics • Contraindication to bupivacaine, paracetamol, ketorolac, oxycodone or morphine • Medical condition that will make it difficult to assess sensory distributions to of peripheral nerves or to communicate with staff • Use of any of the following medications within the times specified before surgery: long-acting opioid medication or NSAIDs (except for low-dose aspirin used for cardioprotection) within 3 days, or any opioid medication within 24 hours • Suspected or known recent history (< 3 months) of drug or alcohol abuse • Concurrent physical condition that may require analgesic treatment (such as NSAID or opioid) in the postsurgical period for pain that is not strictly related to Dupuytren’s contracture and which may confound the postsurgical assessments • Infection at the planned block site • Initiation of treatment with any of the following medications within 1 month of study drug administration or if the medication(s) are being given to control pain: selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), gabapentin, pregabalin (Lyrica®), or duloxetine (Cymbalta®) • Use of dexmedetomidine HCl (Precedex®) within 3 days of study drug administration • Body weight <50 kg (110 pounds) or a body mass index >44 kg/m2 • Uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with study assessments • Any chronic neuromuscular deficit affecting the peripheral nerves or muscles of the surgical extremity • Any chronic condition or disease that would compromise neurological or vascular assessments • Presence of preexisting coagulation disorders • Baseline neurological deficits • History of impaired kidney function, chronic respiratory disease, rheumatoid arthritis, coagulopathy or loss of sensation in the extremities • Malignancy in the last 2 years, with exception of non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix • Previous participation in an EXPAREL study • Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject’s participation in this study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Anesthesia and analgesia for both phases of the treatment with Xiapex in patients with Dupuytren's contracture with a single periferal nerve block. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Investigation will be done every 5 minutes once the block is preformed. Then at timepoint 1h and 1h30. Patients will be contacted after discharge at 24h, 36h, 48h, 60h, 72h, 84h, 96h, 5, 6 and 7 days and 6 weeks after the nerve block. |
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E.5.2 | Secondary end point(s) |
* Numeric rating scale (NRS) * Overall Benefit of Analgesia Score (OBAS) (Lehmann, 2010) * Start and duration of the sensorial block with monitoring of the second phase of the sensorial block * Start and duration of the sensorial block with monitoring of the second phase of the sensorial block motor block * Duration of sleep and sleepquality during the week of intervention * Patient satisfaction concerning analgesia * Functionality of the operated limb * Patient satisfaction * Surgeon satisfaction |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Investigation will be done every 5 minutes once the block is preformed. Then at timepoint 1h and 1h30. Patients will be contacted after discharge at 24h, 36h, 48h, 60h, 72h, 84h, 96h, 5, 6 and 7 days and 6 weeks after the nerve block. |
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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 | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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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Patients can be included within 3 months. Evaluation will take longer untill 3 months after the last patient is included (see timepoints) |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | |