手術後の神経痛の治療におけるQutenza (8% カプサイシン) と低用量カプサイシンの比較 (RISE)
手術後の神経因性疼痛を有する被験者における Qutenza® の有効性と安全性を評価するインターベンショナル、第 III 相、二重盲検、無作為化、対照群、並行グループ、マルチサイト、臨床試験
This is an interventional, Phase III, double-blind, randomized, controlled, parallel-group, multi-site, clinical trial to confirm the efficacy and safety of repeated topical application of Qutenza (capsaicin 8% topical system) versus low-dose capsaicin control (capsaicin 0.04% topical system) in subjects with moderate to severe postsurgical neuropathic pain (PSNP).
調査の概要
詳細な説明
After a Screening Period of up to 19 days, including the Baseline Phase from Day -7 to Day -1, subjects will be allocated to Qutenza or to low-dose capsaicin control topical system (capsaicin 0.04%) at the Randomization Visit. The blinded Treatment Period consists of a Core Phase (Day 1 to Week 12) and an Extension Phase (Week 13 to Week 42), which includes a Follow-up of 14 days
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
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Arizona
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Tucson、Arizona、アメリカ、85712
- Tucson Orthopaedic Institute
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California
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Vista、California、アメリカ、92009
- ILD Research Center
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District of Columbia
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Washington D.C.、District of Columbia、アメリカ、20006
- International Spine, Pain, and Performance Center
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Florida
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Clermont、Florida、アメリカ、34711
- South Lake Pain Institute
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DeLand、Florida、アメリカ、32720
- University Clinical Research - DeLand Clinical Research Unit
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Miami、Florida、アメリカ、33174
- Florida Research Center, Inc.
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Tampa、Florida、アメリカ、33606
- Clinical Research of West Florida
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Georgia
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Marietta、Georgia、アメリカ、30060
- Drug Studies America
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Illinois
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Chicago、Illinois、アメリカ、60612
- Rush University Medical Center
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Kansas
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Overland Park、Kansas、アメリカ、66210
- Neuroscience Research Center, LLC
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Overland Park、Kansas、アメリカ、66211
- Kansas City Bone & Joint Clinic, P.A.
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Massachusetts
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Boston、Massachusetts、アメリカ、02131
- Boston Clinical Trials
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Michigan
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Bay City、Michigan、アメリカ、48706
- Great Lakes Research Group, Inc.
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New Jersey
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Shrewsbury、New Jersey、アメリカ、07702
- Premier Pain Centers
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New York
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New York、New York、アメリカ、10022
- Ainsworth Institute of Pain Management
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North Carolina
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Wilmington、North Carolina、アメリカ、28401
- Accellacare
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Winston-Salem、North Carolina、アメリカ、27103
- The Center for Clinical Research
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Ohio
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Dayton、Ohio、アメリカ、45432
- META Medical Research Institute, LLC
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Pennsylvania
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King of Prussia、Pennsylvania、アメリカ、19406
- Main Line Spine
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Tennessee
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Knoxville、Tennessee、アメリカ、37909
- New Phase Research & Development
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Texas
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Houston、Texas、アメリカ、77079
- Expert Pain
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San Antonio、Texas、アメリカ、78229
- The University of Texas Health Science Center at San Antonio
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Utah
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Salt Lake City、Utah、アメリカ、84107
- Wasatch Clinical Research, LLC
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Aberdeen、イギリス
- Aberdeen Royal Infirmary (ARI) - NHS Grampian
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Coventry、イギリス
- Accellacare
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Leeds、イギリス
- Leeds General Infirmary - Leeds Teaching Hospitals NHS Trust
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Northwood、イギリス
- Accellacare - (MeDiNova Limited) - North London
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Sidcup、イギリス
- MeDiNova South London Quality Research Site
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Northamptonshire
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Corby、Northamptonshire、イギリス
- Accellacare - (MeDiNova Limited) - Northamptonshire
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Yorkshire
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Shipley、Yorkshire、イギリス
- Accellacare - (MeDiNova Limited) - Yorkshire
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Amsterdam、オランダ
- VUMC
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Beek、オランダ
- PT&R
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Hengelo、オランダ
- NOCEPTA
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Leiden、オランダ
- Leiden University Medical Center (LUMC)
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Alicante、スペイン
- Hospital General Universitario de Alicante
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Barcelona、スペイン
- Hospital Del Mar
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L'Hospitalet de Llobregat、スペイン
- Hospital Universitario de Bellvitge
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Madrid、スペイン
- Hospital Universitario de La Princesa
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Madrid、スペイン
- Hospital Universitario La Moraleja
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Málaga、スペイン
- Hospital Quironsalud Malaga
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Pamplona、スペイン
- Clinica Universidad de Navarra
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Santiago de Compostela、スペイン
- Clinica Gaias
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Valencia、スペイン
- Hospital Clinico Universitario de Valencia
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Valladolid、スペイン
- Hospital Clinico Universitario de Valladolid
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Amiens、フランス
- CHU Amiens Picardie
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Angers、フランス
- Centre Regional De Lutte Contre Le Cancer (Crlcc) -Centre Paul Papin
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Cahors、フランス
- Centre Hospitalier Jean Rougier
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Clermont-Ferrand、フランス
- Centre Hospitalier Universitaire de Clermont Ferrand
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Lille、フランス
- Centre Hospitalier Regional Universitaire (CHRU) de Lille - Hopital Claude Huriez
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Limoges、フランス
- Clinique Francois Chenieux
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Paris、フランス
- Cochin Hospital-Paris Descartes University
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Paris、フランス
- Groupe Hospitalier Paris saint-Joseph
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Poitiers、フランス
- CHU Poitiers / La Miletrie
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Pays de la Loire Region
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La Roche-sur-Yon、Pays de la Loire Region、フランス
- Centre Hospitalier Departemental Vendee - Centre d'evaluation et de Traitement de la Douleur
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Nantes、Pays de la Loire Region、フランス
- CHU de Nantes - Hopital Nord Laennec
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Bialystok、ポーランド
- Vitamed Nzoz Im. Edyty Jakubow
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Katowice、ポーランド
- Nzoz Neuro-Medic
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Krakow、ポーランド
- Linden Centrum Medyczne
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Oświęcim、ポーランド
- Instytut Zdrowia dr Boczarska-Jedynak
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Warsaw、ポーランド
- Centrum Badan Medycznych Nigrir
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Wroclaw、ポーランド
- FutureMeds sp. z o. o.
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Świdnik、ポーランド
- Lubelskie Centrum Diagnostyczne
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Silesian Voivodeship
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Katowice、Silesian Voivodeship、ポーランド
- Centrum Medyczne Pratia Katowice
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Katowice、Silesian Voivodeship、ポーランド
- Silmedic Sp z o.o. Oddzial w Katowicach
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
General
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The subject has given written informed consent to participate.
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Female or male subjects aged 18 years or older.
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For women of childbearing potential: negative pregnancy tests at Screening Visit (Visit 1), the Randomization Visit (Visit 2), and prior to each reapplication of the investigational medicinal product (IMP), and must have agreed to practice medically acceptable methods of birth control.
Confirmation of diagnosis of chronic moderate to severe PSNP
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Documented diagnosis of PSNP by the following criteria:
- A history of post-surgical pain with a duration of at least 6 months to maximally 60 months that is plausibly related to the surgical intervention as documented on a body map.
- Douleur Neuropathique 4 interview (DN4i) of at least 3 out of 7 points at Visit 1.
- The pain must extend beyond the scar area to neuroanatomically adjacent skin areas and be related to the site of the surgery.
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Documented diagnosis of probable or definite PSNP according to the following criteria (Finnerup et al. 2016):
- The pain must be associated with sensory signs in the same neuroanatomically plausible distribution. The area of sensory changes may extend beyond, be within, or overlap with the area of pain (criterion for probable neuropathic pain), or
- In addition to 5a : Direct surgical evidence (e.g., surgeon´s clear verification of an intraoperative nerve lesion) (criterion for definite neuropathic pain).
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The subject has moderate to severe pain with a baseline value for 24-hr average pain intensity of at least 4 points on the NPRS. The baseline value is calculated as the average of the 24-hr average pain intensity ratings of the Baseline Phase (Day -7 to Day -1). At least 5 (out of the last 7 days) pain ratings should be available during the Baseline Phase. If less than 5 pain ratings are available in the last 7 days, the subject may be rescheduled for Visit 2 (1 time only) after having received appropriate re-training in the use of the e-diary to ensure compliance.
Suitability for treatment with IMP
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The size of the affected painful intact skin area is not larger than the size of 4 standard Qutenza topical systems (1120 cm2).
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The skin in the area where the IMP will be applied, and that may also contain the scar tissue, is intact, dry, and non-irritated (i.e., there are no signs and symptoms of skin disease, skin irritation, inflammation or injury, such as active herpes zoster lesions, atopic dermatitis, ulceration, wounds). This is reflected by a dermal assessment score of 0 = "no evidence of irritation" or 1 = "minimal erythema, barely perceptible".
Eligibility with regard to protocol adherence, to allowed pre-treatments and concomitant treatments
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The subject is willing to adhere to the restricted use of concomitant treatments .
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The subject experiencing pain is:
- currently not receiving treatment for PSNP or
- receives a stable systemic treatment for PSNP that started more than 30 days prior to the Randomization Visit (Visit 2).
Non-exhaustive list of examples of types of surgeries with resulting PSNP:
Thoracic surgery Breast surgery Abdominal surgery (cholecystectomy, appendectomy) Donor nephrectomy Gynecologic surgery (hysterectomy, C-section) Varicose vein surgery Inguinal herniotomy Lipoma removal Knee surgery Knee arthroplasty Ankle surgery
Exclusion Criteria:
General or previous treatments
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The subject received Qutenza before the Randomization Visit (Visit 2) or received a medical device in another clinical trial within 7 days before the Randomization Visit (Visit 2), or
- Any former use of topical capsaicin in the area of the PSNP before Visit 2, except for the use of a low-dose (<1%) capsaicin product - but not within 7 days before Visit 2.
- The subject participated previously in this clinical trial or participated in another clinical trial for the treatment of PSNP completing less than 3 months ago.
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A score of 0 out of 5 in all 3 categories of the neurological/sensory examinations, i.e., for warm sensation, pinprick and cold sensation at the Screening Visit (Visit 1).
Confounding factors
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The subject reported a 24-hr average pain intensity score of 10 on the NPRS for at least 4 days during the Baseline Phase.
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Any painful procedure planned during the course of the trial that may, in the opinion of the investigator, affect the efficacy or safety assessments.
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Subjects with PSNP related to a surgery/condition with a high potential for confounding symptoms, e.g., the pain is at least partially due to pain in deeper structures such as muscles or bones (including referred pain from deeper structures) as listed in examples.
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Other painful conditions in the body area that is affected by PSNP and may affect efficacy or safety assessments and cannot be discriminated from the target pain by the subject, including infectious, non-infectious, inflammatory or neuropathic conditions which could also be complications related to the previous surgical procedure.
Non-exhaustive list of examples of types of surgeries/conditions not suitable for eligibility Any surgery performed due to suspected neoplasia: suspected residual neoplasia or metastases Conditions where nociceptive or neuropathic pain has been the reason for the surgery, e.g., failed back surgery, carpal tunnel syndrome or other nerve compression syndromes leading to neuropathic pain, (e.g., meralgia paresthetica) Conditions of projected neuropathic pain (i.e., from inguinal hernia repair) with painful symptoms in the genital region, e.g., the scrotum or vagina Amputations Radicular pain and nerve trunk lesions Scar pain neuroma Complex Regional Pain Syndrome (Type I or Type II)
Contraindications to IMP
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Neuropathic pain areas located only on the face, above the hairline of the scalp, and/or in proximity to mucous membranes.
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Hypersensitivity to capsaicin (i.e., chili peppers or over-the-counter [OTC] capsaicin products), or to any excipients of the IMP or to excipients of the cleansing gel in use and their components, or to topical anesthetics in use and their components.
Medical history/concurrent condition(s)/other factors
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Pending litigation due to chronic pain or disability.
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The subject has a history of alcohol or drug abuse or is actively abusing drugs (including alcohol, medication) during the 1 year prior to the Screening Visit (Visit 1) as judged by the investigator.
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Evidence or history of severe psychiatric illness/disorder during the 3 years prior to the Screening Visit (Visit 1) that, in the investigator's opinion, may affect efficacy or safety assessments or may compromise the subject's safety during trial participation, e.g., major depression, major anxiety disorder, psychosis, severe personality disorders.
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Evidence of cognitive impairment including dementia that may interfere with the subject's ability to complete pain assessments requiring recall of the average pain level in the past 24 hrs.
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Surgical intervention in the last 3 months preceding the Screening Visit (Visit 1) if it is affecting the efficacy or safety assessments, or any scheduled or planned surgery during the trial, with the exception of the Extension Phase if the planned surgery is not expected to affect the efficacy or safety assessments.
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Patients with current clinically significant disease(s) or condition(s) (including clinically significant cardiovascular disease and/or significant pain in other areas) that may affect efficacy or safety assessments, or any other reason which, in the investigator's opinion, may preclude the subject's participation in the full duration of the trial. Patients with current signs and symptoms consistent with Coronavirus disease 2019 (COVID-19) (e.g., dry cough, dyspnea, sore throat, fatigue, fever) or patients who had those symptoms within the last 14 days prior to screening and had a positive SARS-CoV2 PCR test result.
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Unstable or poorly controlled blood pressure which, in the opinion of the investigator, would put the subject at risk of severe adverse blood pressure increases upon IMP application.
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Known or suspected of not being able to comply with the requirements of the trial protocol or the instructions of the trial site staff.
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Not able to communicate meaningfully with the trial site staff.
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The subject is an employee of the investigator or trial site, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial site, or is a family member of the employees or the investigator.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Qutenza (capsaicin) 8% topical system
Qutenza (capsaicin 8% topical system, containing capsaicin 179 mg or capsaicin 640 µg/cm2 of topical system) |
High concentration capsaicin |
|
アクティブコンパレータ：Low-dose capsaicin control
capsaicin 0.04% topical system |
Low-dose capsaicin control |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change From Baseline in the 24-Hour Average Pain Intensity (API) Between Week 2 and Week 12 [Core Phase]
時間枠：From the Baseline Phase (Day -7 to Day -1) to Visit 6 (Week 12/Day 84).
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NOTES:
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From the Baseline Phase (Day -7 to Day -1) to Visit 6 (Week 12/Day 84).
|
|
Change From Baseline in the 24-Hour API to Week 12 [Core Phase]
時間枠：From the Baseline Phase (Day -7 to Day -1) to Visit 6 (Week 12/Day 84).
|
NOTES:
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From the Baseline Phase (Day -7 to Day -1) to Visit 6 (Week 12/Day 84).
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change From Baseline in the 24-Hour API Between Week 2 and Week 42 [Extension Phase]
時間枠：Baseline Phase (Day -7 to Day -1) up to the Final Visit (Week 42/Day 294).
|
NOTES:
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Baseline Phase (Day -7 to Day -1) up to the Final Visit (Week 42/Day 294).
|
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Change From Baseline in the 24-Hour API at Week 42 [Extension Phase]
時間枠：Baseline Phase (Day -7 to Day -1) up to the Final Visit (Week 42/Day 294).
|
NOTES:
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Baseline Phase (Day -7 to Day -1) up to the Final Visit (Week 42/Day 294).
|
|
Change From Baseline in Treatment Area Size at Week 12 [Core Phase]
時間枠：From Visit 2 (Day 1, before IMP application) to Visit 6 (Week 12/Day 84, before IMP application).
|
Treatment area size was measured in square centimeters (cm²) and comprised the area identified by the participant as the usually most painful area(s), and/or the area characterized by dynamic mechanical allodynia (DMA), and/or the area of pinprick hyperalgesia. Treatment area size was assessed at Visit 2 (Day 1) before IMP application and at Visit 6 (Week 12/Day 84) before IMP application. The outcome was the change from baseline to Week 12 in treatment area size. A negative change indicates a reduction in treatment area size. |
From Visit 2 (Day 1, before IMP application) to Visit 6 (Week 12/Day 84, before IMP application).
|
|
Change From Baseline in Treatment Area Size at Week 42 [Extension Phase]
時間枠：From baseline to the Final Visit at Week 42.
|
Treatment area size was measured in square centimeters (cm²) and comprised the area identified by the participant as the usually most painful area(s), and/or the area characterized by dynamic mechanical allodynia (DMA), and/or the area of pinprick hyperalgesia. The outcome was the change from baseline to the Final Visit at Week 42 in treatment area size. A negative change indicates a reduction in treatment area size. |
From baseline to the Final Visit at Week 42.
|
|
Incidence of Treatment-Emergent Adverse Events (TEAEs) [Core Phase]
時間枠：Visit 2 (Day 1) up to Visit 6 (Week 12/Day 84)
|
Documentation of TEAEs (Safety and tolerability) from the start of treatment at Visit 2 (Day 1) up to the end of the Core Phase of the Treatment Period. |
Visit 2 (Day 1) up to Visit 6 (Week 12/Day 84)
|
|
Incidence of TEAEs Leading to Discontinuation From Trial [Core Phase]
時間枠：Visit 2 (Day 1) up to Visit 6 (Week 12/Day 84)
|
Documentation of TEAEs (Safety and tolerability) from the start of treatment at Visit 2 (Day 1) up to the end of the Core Phase of the Treatment Period. |
Visit 2 (Day 1) up to Visit 6 (Week 12/Day 84)
|
|
Incidence of TEAEs [Extension Phase]
時間枠：Visit 2 (Day 1) up to Final Visit (Week 42/Day 294)
|
Documentation of TEAEs (Safety and tolerability) from the start of treatment at Visit 2 (Day 1) up to the end of the Extension Phase. |
Visit 2 (Day 1) up to Final Visit (Week 42/Day 294)
|
|
Incidence of TEAEs Leading to Discontinuation From Trial [Extension Phase]
時間枠：Visit 2 (Day 1) up to Final Visit (Week 42/Day 294)
|
Documentation of TEAEs (Safety and tolerability) from the start of treatment at Visit 2 (Day 1) up to the end of the Extension Phase. |
Visit 2 (Day 1) up to Final Visit (Week 42/Day 294)
|
協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。