Ultrasound-assisted or Landmark-based Intrathecal Administration of Nusinersen in Adult Patients With Spinal Muscular Atrophy (The EchoSpin Study)

Spinal Muscular Atrophy Clinical Trial

— EchoSpin  

Official title:

Interlaminar Ultrasound-assisted or Landmark-based Intrathecal Administration of Nusinersen in Adult Patients With Spinal Muscular Atrophy: a Retrospective Analysis of More Than 500 Consecutive Administrations

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05644899
• Other study ID #: EchoSpin
• Status: Completed
• Start date: December 16, 2022
• Est. completion date: January 10, 2023

Study information

• Verified date: December 2022
• Source: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Nusinersen (Spinraza, Biogen Inc, Boston, MA), the first treatment approved by FDA and EMA for all Spinal Muscular Atrophy (SMA) subtypes, is an antisense oligonucleotide that is administered intrathecally through a lumbar puncture. This procedure can be challenging in some adults with intermediate and late onset SMA (types II-IV) frequently presenting scoliosis secondary to neuromuscular weakness and often treated with spinal instrumentation to prevent worsening deformities. In such patients, in order to access the intrathecal space, US guidance and/or assistance have been recently proposed as useful and successful tool. The US guidance and/or assistance have been associated to a high success rate, a reduction of number of attempts and needle passes to obtain a successful anesthesia. A reduced risk of adverse events (AEs), such as post dural puncture headache (PDPH) and low back pain (LBP), and low patient satisfaction often associated with multiple needle punctures was also reported. Aim of this retrospective study was to report the efficacy, evaluated as rate of the successful procedures and subsequent delivery of nusinersen within the subarachnoid space, the number of attempts, the procedure time and the adverse events (AEs) of interlaminar intrathecal nusinersen administration using either ultrasound assistance or the landmark-based technique in a historical cohort of 51 adult SMA patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: January 10, 2023
• Est. primary completion date: January 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• A genetically confirmed diagnosis of SMA
• Treatment with nusinersen

Exclusion Criteria:

• congenital coagulopathy,
• localized infections,
• increased intracranial pressure.

Related Conditions & MeSH terms

• Anesthesia, Spinal
• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy
• Spinal Puncture Complications
• Ultrasonography

Intervention

Procedure:
• Interlaminar ultrasound-assisted intrathecal administration of nusinersen
All procedures were performed with patients either seated or placed in a lateral decubitus. After skin disinfection with 2% chlorhexidine in 70% alcohol, using a convex array, the L3-4 or L4-5 intervertebral space was identified and a left paramedian sagittal oblique view was obtained; the probe was rotated 90° into a transverse orientation, centered on the neuraxial midline, and moved in either the cephalad or caudal direction to obtain a transverse interlaminar view; the intersection between the two markings of the spinal midline and interspinous space was identified as the spinal entry point of the needle. After local anesthesia (LA) with lidocaine 2%, a 25-gauge non-traumatic 90 mm Whitacre spinal needle or a traumatic 90 mm Quincke spinal needle was used to access the subarachnoid space. After confirmation of cerebrospinal fluid (CSF) flow, 5 mL of CSF were removed. Subsequently, nusinersen was administered intrathecally over 1-3 min.
• Landmark-based intrathecal administration of nusinersen
All procedures were performed with patients placed in their most comfortable position (either seated or placed in a lateral decubitus). After skin disinfection with 2% chlorhexidine in 70% alcohol, conventional palpation of the superior aspect of iliac crest was performed and the palpated intercristal line was assumed to cross the spine at L4 vertebral body or L4-L5 interspace. The skin was marked with horizontal and vertical lines at the L3-L4 or L2-L3 interspaces and was referred as entry point of the needle. The procedure was then completed in the same fashion as for US-assisted technique.

Locations

Country	Name	City	State
Italy	Fondazione Policlinico Gemelli	Roma	RM

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of successful administrations	Defined as a confirmation of the CSF flow through the spinal needle and subsequent administration of whole drug	During the procedure
Primary	Number of attempts	Defined as the number of needle insertions through the skin surface	During the procedure
Primary	Procedure time	The time in minutes from the start of US imaging or the palpation of superior aspect of iliac crest to visualization of CSF flow	During the procedure
Primary	Number of technical success procedures	Defined as a successful intrathecal administration with equal or less than 4 attempts	During the procedure
Primary	Adverse events (AEs)	Defined as mild AEs (Post Dural Puncture Headache, Low Back Pain) or severe AEs (spinal cord injury/epidural hematoma, abdominal organ lesions)	In the first 72 hours after the procedure