Clinical trial NCT05306548: A Norwegian Trial Comparing Treatment Strategies for Carpal Tunnel Syndrome
Official title: The NOR-CACTUS Trial - A Norwegian Trial Comparing Treatment Strategies for Carpal Tunnel Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Carpal Tunnel Syndrome
Keywords: Surgery
Corticosteroid injection
Ultrasound guided intervention
Nerve conduction studies
Randomized controlled trial
Lead sponsor: Diakonhjemmet Hospital
Sponsor class: OTHER
Collaborators: name: Oslo University Hospital
name: Martina Hansen's Hospital
name: South-Eastern Norway Regional Health Authority
name: University Hospital, Akershus
First posted: 2022-04-01
Enrollment: 258
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two-arm, prospective, multi-center, parallel-group, open-label assessor-blinded non-inferiority treatment strategy study
Primary purpose: TREATMENT

Brief summary: Carpal tunnel syndrome (CTS) causes numbness and pain in the hand and arm, and is an important cause of work absence and disability. The aim of the NOR-CACTUS Trial is to compare outcomes of a treatment strategy where the initial treatment is up to two ultrasound-guided corticosteroid injections, followed by scheduled clinical assessment of treatment effect, and subsequent surgery if needed, to a treatment strategy where surgery is the first-line treatment. Participants will be randomized to one of the treatment strategies, and followed up for two years after start of the study intervention. Outcomes will include patient-reported, clinical, functional and neurophysiological measures, and health-economic aspects. The hypothesis of the study is that there is no difference between the two treatment groups in the percentage of patients with a satisfactory symptom relief (treatment success) one year after the initial therapeutic intervention.

Detailed description: CTS is the most common non-traumatic hand disorder, prevalent in approximately 4% of the adult population. The condition may have a substantial impact on an individual's quality of life, ability to accomplish activities of daily living, and to perform occupational duties. Associated healthcare costs represent a significant socioeconomic burden.

Currently, many patients with mild and moderate CTS treated surgically without a preceding trial of less invasive non-surgical therapies. An increase in the use of non-surgical first-line therapies (e.g. corticosteroid injection into the carpal tunnel), while reserving surgery for refractory cases, aim to optimize the trade-off between treatment risk and benefit, while also ensuring appropriate use of health resources. However, there is a lack of studies directly comparing the efficacy of corticosteroid injections to surgery, and the long-term safety of corticosteroid injections has not been investigated.

It is not well-known if patients who are initially treated with corticosteroid injections will eventually need to proceed to surgery, and therefore may have to endure the symptoms for a longer period of time, with potentially worse long-term outcomes, compared to patients who has surgery as first-line treatment. On the other hand, it is not beneficial if patients are unnecessarily exposed to the risks associated with surgery, if symptoms could have been satisfactory resolved with a non-surgical method.

The current study will assess if first-line treatment with up to two ultrasound-guided corticosteroid injections is non-inferior to surgery with regards to treatment success. A less invasive treatment approach might result in important benefits to the patient, e.g. less pain, reduced risk of complications, and faster return to work and activities. This might also be of importance to family members, as many CTS patients are at an age where they have care responsibilities. Non-surgical treatments might benefit society by decreasing work absence and reducing health expenditure, and allowing better access to surgical services for other patient groups. High quality documentation is needed to provide a base for future treatment guidelines. Evidence based clinical guidelines provide treatment decision support and help reduce national and regional differences in treatment practices, and ensure that all patients have equal access to evidence-based treatment.

In the NOR-CACTUS trial, adult individuals with idiopathic CTS of a mild-to-moderate degree will be randomized to receive either A) Primary open surgical carpal tunnel release, or B) Up to two ultrasound-guided corticosteroid (triamcinolone hexacetonide) injections in the carpal tunnel, and subsequent open surgical carpal tunnel release in case of unsatisfactory treatment result. Participants will be randomized to receive one of the treatment strategies, and followed for two years, with the primary endpoint being successful treatment result one year after start of the intervention.

The hypothesis of the study is that the percentage of patients with a satisfactory symptom relief (treatment success) one year after the initial therapeutic intervention in the injection treatment strategy arm is non-inferior to that of the surgery treatment arm. The primary outcome is based on the disease-specific patient-reported outcome Boston Carpal Tunnel Questionnaire (BCTQ) symptom severity scale (SSS). Further outcomes will include other patient-reported, clinical, functional and neurophysiological measures, and health-economic aspects.

Eligibility criteria: Inclusion Criteria:

1. Adult (≥18 years of age)
2. Patient history indicating CTS
3. Neurophysiological examination performed within 6 months
4. Diagnosis of CTS based on:

   1. Classic/probable or possible symptoms, and neurophysiological findings consistent with CTS

      Or, in case of normal neurophysiological findings:
   2. Classic/probable symptoms and positive physical exam findings and/or nighttime symptoms
5. Mild to moderate symptoms (intermittent, interfering with everyday life, and/or disturb sleep)

Exclusion Criteria:

1. Previous CTS surgery or corticosteroid injection in the carpal tunnel in the relevant hand
2. Diagnosis of severe CTS, based on history and examination indicating severe CTS with constant symptoms including pain, loss of sensibility, dexterity or reduced temperature sensation, weakness of thumb abduction and opposition, or atrophy of thenar musculature. Disappearance of pain may indicate permanent sensory loss.
3. History suggesting underlying causes of CTS e.g. inflammatory wrist arthritis and/or flexor tenosynovitis
4. Previous significant trauma or fracture, deformity or tumor in the wrist or hand in the relevant hand
5. Presence of conditions affecting a normal nerve function e.g. cervical disc herniation, polyneuropathy or previous nerve injury
6. Major co-morbidities, such as severe malignancies, severe or uncontrolled infections, uncontrollable hypertension, severe cardiovascular disease (NYHA class III or IV) and/or severe respiratory diseases, severe renal failure, active ulcus ventriculi, leukopenia and/or thrombocytopenia
7. Severe psychiatric or mental disorders
8. Local infection or wound in the affected hand/wrist
9. Any other medical condition that according to the treating physician and/or local guidelines makes adherence to treatment protocol impossible
10. Inadequate birth control1, pregnancy2, and/or breastfeeding (current at screening or planned within the duration of the study)
11. Known hypersensitivity to Triamcinolone Hexacetonide (Lederspan) or any of the excipients (sorbitol, polysorbate or benzyl alcohol)
12. Concomitant therapy with CYP3A-inhibitors or digitalis glycosides
13. Patients vaccinated or immunized with live virus vaccines within 2 weeks of treatment
14. Alcohol or other substance abuse
15. Language barriers
16. Other factors which make adherence to study protocol impossible

Primary outcomes:
measure: Successful treatment result after 12 months
timeFrame: 12 months
Secondary outcomes:
measure: Successful treatment result after 3 months
timeFrame: 3 months
measure: Successful treatment result after 6 months
timeFrame: 6 months
measure: Successful treatment result after 24 months
timeFrame: 24 months
measure: Boston Carpal Tunnel Questionnaire Symptom Severity Scale
timeFrame: 0-24 months
measure: Boston Carpal Tunnel Questionnaire Functional Status Scale
timeFrame: 0-24 months
measure: Nerve conduction studies: Motor median nerve distal latency
timeFrame: 0 and 12 months
measure: Nerve conduction studies: Motor median nerve proximal latency
timeFrame: 0 and 12 months
measure: Nerve conduction studies: Motor median nerve amplitude
timeFrame: 0 and 12 months
measure: Nerve conduction studies: Motor median nerve conduction velocity
timeFrame: 0 and 12 months
measure: Nerve conduction studies: Motor ulnar nerve distal latency
timeFrame: 0 and 12 months
measure: Nerve conduction studies: Motor ulnar nerve proximal latency
timeFrame: 0 and 12 months
measure: Nerve conduction studies: Motor ulnar nerve amplitude
timeFrame: 0 and 12 months
measure: Nerve conduction studies: Motor ulnar nerve conduction velocity
timeFrame: 0 and 12 months
measure: Nerve conduction studies: Sensory median nerve latency
timeFrame: 0 and 12 months
measure: Nerve conduction studies: Sensory median nerve amplitude
timeFrame: 0 and 12 months
measure: Nerve conduction studies: Sensory median nerve conduction velocity
timeFrame: 0 and 12 months
measure: Nerve conduction studies: Sensory ulnar nerve latency
timeFrame: 0 and 12 months
measure: Nerve conduction studies: Sensory ulnar nerve amplitude
timeFrame: 0 and 12 months
measure: Nerve conduction studies: Sensory ulnar nerve conduction velocity
timeFrame: 0 and 12 months
measure: Electromyography: Spontaneous activity
timeFrame: 0 and 12 months
measure: Electromyography: Chronic neurogenic changes
timeFrame: 0 and 12 months
measure: Nerve conduction studies: Bland score
timeFrame: 0 and 12 months
measure: Semmes-Weinstein monofilament test
timeFrame: 0-24 months
measure: Grip strength
timeFrame: 0-24 months
measure: Grip ability test (GAT)
timeFrame: 0-24 months
measure: Patient assessment of treatment effect on symptoms
timeFrame: 3-24 months
measure: Patient assessment of expected treatment effect on symptoms
timeFrame: 0 months
measure: Patient assessment of CTS symptoms
timeFrame: 0-24 months
measure: Patient assessment of CTS-related functional impairment
timeFrame: 0-24 months
measure: Patient assessment of acceptability of CTS-related symptoms and functional disability
timeFrame: 0-24 months
measure: Ultrasound measure of proximal cross-sectional area of the median nerve
timeFrame: 0-24 months
measure: Ultrasound measure of distal cross-sectional area of the median nerve
timeFrame: 0-24 months
measure: Ultrasound measures of vascularity of the median nerve in the carpal tunnel
timeFrame: 0-24 months
measure: Disabilities of the Arm, Shoulder, and Hand (Quick-DASH)
timeFrame: 0-24 months
measure: Patient pain assessment
timeFrame: 0-24 months
measure: Work Productivity and Activity Impairment Questionnaire (WPAI)
timeFrame: 0-24 months
measure: Days of work absence since start of intervention
timeFrame: 3-24 months
measure: EuroQoL 5-dimension health-related quality of life (EQ5D-5L)
timeFrame: 0-24 months
measure: Adverse events
timeFrame: 0-24 months
measure: Successful treatment after 1 corticosteroid injection
timeFrame: 3-24 months
measure: Successful treatment after 2 corticosteroid injections
timeFrame: 3-24 months
measure: Successful treatment after secondary surgery
timeFrame: 3-24 months
measure: Undergone re-operation
timeFrame: 3-24 months
measure: Cost of treatment
timeFrame: 0-24 months
Other outcomes:
measure: Use of hospital services
timeFrame: 0-24 months
measure: Use of primary care resources
timeFrame: 0-24 months
measure: Work participation
timeFrame: 0-24 months
measure: Total cost
timeFrame: 0-24 months
measure: Environmental impact analysis
timeFrame: 0-24 months
Locations:
city: Oslo
country: Norway
facility: Department of Surgery and Anesthesiology, Diakonhjemmet Hospital
state: Norge
city: Lørenskog
country: Norway
facility: Akershus University Hospital
state: Viken
city: Oslo
country: Norway
facility: Department of Rheumatology, Diakonhjemmet Hospital
city: Sandvika
country: Norway
facility: Department of Orthopedic Surgery, Martina Hansens Hospital
city: Sandvika
country: Norway
facility: Department of Rheumatology, Martina Hansens Hospital
Study officials:
affiliation: Diakonhjemmet Hospital
name: Hilde B Hammer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bland JD. A neurophysiological grading scale for carpal tunnel syndrome. Muscle Nerve. 2000 Aug;23(8):1280-3. doi: 10.1002/1097-4598(200008)23:83.0.co;2-y.
citation: Levine DW, Simmons BP, Koris MJ, Daltroy LH, Hohl GG, Fossel AH, Katz JN. A self-administered questionnaire for the assessment of severity of symptoms and functional status in carpal tunnel syndrome. J Bone Joint Surg Am. 1993 Nov;75(11):1585-92. doi: 10.2106/00004623-199311000-00002.
citation: Beaton DE, Wright JG, Katz JN; Upper Extremity Collaborative Group. Development of the QuickDASH: comparison of three item-reduction approaches. J Bone Joint Surg Am. 2005 May;87(5):1038-46. doi: 10.2106/JBJS.D.02060.
citation: Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics. 1993 Nov;4(5):353-65. doi: 10.2165/00019053-199304050-00006.
citation: Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, Bonsel G, Badia X. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011 Dec;20(10):1727-36. doi: 10.1007/s11136-011-9903-x. Epub 2011 Apr 9.