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

NCT05644899 | Completed

• 1 other identifier: EchoSpin
• Study Type: observational
• Target: 51
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (5)

• 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

• Number of attempts

  Defined as the number of needle insertions through the skin surface

  During the procedure

• 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

• Number of technical success procedures

  Defined as a successful intrathecal administration with equal or less than 4 attempts

  During the procedure

• 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

Study Arms (1)

SMA patients

51 adults with a genetically confirmed diagnosis of SMA (13 SMA type 2, 38 SMA type 3) treated with nusinersen. The technique used was based on the anesthesiologist's preference.

Procedure: Interlaminar ultrasound-assisted intrathecal administration of nusinersen; Procedure: Landmark-based intrathecal administration of nusinersen

Interventions

Interlaminar ultrasound-assisted intrathecal administration of nusinersen PROCEDURE

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.

SMA patients

Landmark-based intrathecal administration of nusinersen PROCEDURE

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.

SMA patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

51 adults with a genetically confirmed diagnosis of SMA (13 SMA type 2, 38 SMA type 3) consecutively treated with nusinersen intrathecal administration between April 2018 and August 2022 in "Policlinico A. Gemelli" in Rome.

You may qualify if:

• A genetically confirmed diagnosis of SMA
• Treatment with nusinersen

You may not qualify if:

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

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Gemelli

Roma, RM, Italy

Location

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Study Officials

• Bruno A Zanfini

  Fondazione Policlinico A. Gemelli

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2022
• First Posted: December 9, 2022
• Study Start: December 16, 2022
• Primary Completion: January 10, 2023
• Study Completion: January 10, 2023
• Last Updated: March 9, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)