Non-Thermal Plasma to Reduce Recurrence in Chronic Subdural Hematoma

June 16, 2026 updated by: Benjamín Gonzalo Rodríguez Méndez

Application of Non-Thermal Plasma in the Surgical Bed of Chronic Subdural Hematoma to Reduce the Post-Drainage Recurrence Rate: A Randomized Controlled Trial

The goal of this randomized controlled trial is to evaluate whether the adjuvant application of non-thermal plasma (NTP) during standard surgical drainage of chronic subdural hematoma (cSDH) can reduce the recurrence rate at 6 months. The main questions it aims to answer are:

  • Does NTP application significantly lower the radiological and clinical recurrence rate of cSDH compared to surgery alone?
  • Is NTP safe when applied to the subdural space and surgical wound bed?
  • Does NTP improve functional outcomes and time to hematoma resolution?

Participants will be randomly assigned to one of two groups:

  • Experimental group (n = 20): Standard burr hole drainage or craniotomy plus intraoperative NTP application over the exposed dura mater, the residual membrane, soft tissue layers, and the skin incision.
  • Control group (n = 20): Standard surgical drainage alone (no NTP).

Follow-up includes clinical assessments and computed tomography (CT) scans at 1 week, 3 months, and 6 months post-surgery. The primary outcome is recurrence (symptomatic reaccumulation requiring re-intervention or ≥50% volume increase on CT).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, randomised, controlled, parallel-group trial conducted at the ISSEMYM Medical Centre Toluca, "Lic. Arturo Montiel Rojas" (Metepec, State of Mexico, Mexico), in collaboration with the National Institute of Nuclear Research (ININ, Ocoyoacac, State of Mexico, Mexico). The study aims to evaluate the efficacy and safety of intraoperative non-thermal plasma (NTP) application as an adjunct to standard surgical drainage for chronic subdural hematoma (cSDH).

The pathophysiology of cSDH recurrence is driven by the residual vascular parietal membrane (neomembrane), which maintains chronic inflammation, fragile neoangiogenesis, and recurrent microhemorrhages. Standard burr hole drainage or craniotomy evacuates the liquid collection but does not neutralise this biological substrate. Preclinical and clinical evidence suggest that NTP, through controlled delivery of reactive oxygen and nitrogen species (RONS), exerts local anti-inflammatory and pro-regenerative effects. Therefore, NTP applied directly to the subdural space and surgical wound bed may modulate the pathological membrane and reduce recurrence rates.

Eligible patients (≥18 years) with symptomatic cSDH requiring surgery will be randomised 1:1 to either the control group (standard surgery alone) or the experimental group (standard surgery + NTP). Randomisation will be performed using a computer-generated sequence with sealed opaque envelopes. The treating neurosurgeon cannot be blinded due to the nature of the intervention, but the neuroradiologist assessing follow-up CT scans will be blinded to group allocation.

The NTP device (13.56 MHz RF generator, 20 Watts, helium gas at 0.5 LPM) will be operated by trained biomedical personnel from ININ under direct neurosurgical supervision. Application protocol:

  • Subdural space: NTP applied to the exposed dura mater and any visible residual membrane for 60 seconds per 5 cm² at 5 mm distance.
  • Soft tissue layers: sequential application during closure of the periosteum and subcutaneous tissue (same parameters).
  • Skin incision: final application after skin closure.

The control group receives identical surgical treatment without NTP. Both groups receive standard perioperative care, including antibiotics and pain management as per institutional protocol.

Follow-up visits are scheduled at 1 week (± 2 days), 3 months (± 2 weeks), and 6 months (± 2 weeks) post-surgery. At each visit, the clinical assessment includes the Glasgow Coma Scale (GCS), the Modified Rankin Scale (mRS), and documentation of any adverse events. Non-contrast head CT scans are performed at all three time points. The primary endpoint - recurrence - is defined as symptomatic reaccumulation requiring surgical re-intervention OR an asymptomatic volume increase ≥50% on CT scan. Secondary endpoints include time to ≥50% radiological resolution, change in mRS, and safety (adverse events).

The protocol has been approved by the Health Research and Research Ethics Committee (approval number UEeIM.282/25). Written informed consent will be obtained from all participants or their legal representatives. The study is conducted in accordance with the Declaration of Helsinki and Mexican health regulations. Data confidentiality is maintained through coding and secure storage. Participants may withdraw at any time without affecting their medical care. ININ provides the NTP equipment, gas, and technical personnel. ISSEMYM provides surgical resources, hospital facilities, and clinical follow-up. No commercial funding is involved. Results will be disseminated via peer-reviewed publications and scientific conferences, regardless of the outcome.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Mexico
    • State of Mexico
      • Ocoyoacac, State of Mexico, Mexico, 52750
        • Recruiting
        • Plasma Physics Laboratory, National Institute of Nuclear Research
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults ≥ 18 years of age
  • Diagnosis of symptomatic chronic subdural hematoma (cSDH) requiring surgical drainage (burr hole drainage or craniotomy)
  • Ability to provide written informed consent (or consent from legal representative if patient is incapacitated)

Exclusion Criteria:

  • Pure acute or subacute subdural hematoma
  • Uncontrolled coagulopathy or bleeding disorder
  • History of intracranial aneurysm or prior cerebrovascular event with residual deficit
  • Presence of active intracranial metallic implants or electronic devices (e.g., programmable shunt, cardiac pacemaker, deep brain stimulator) in the head region
  • Pregnancy or lactation
  • Participation in another interventional clinical trial within 30 days prior to screening

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard Surgery Alone (Control)
Participants randomised to this arm will receive standard surgical drainage for chronic subdural hematoma according to the routine protocol at ISSEMYM Medical Centre, Toluca. The procedure consists of burr hole drainage or craniotomy under general anaesthesia, complete evacuation of the subdural fluid collection, and placement of a subdural drain if the surgeon considers it necessary. The wound is then closed in anatomical layers. No non-thermal plasma or any other experimental intervention is applied. All participants receive standard perioperative care, including prophylactic antibiotics, pain management, and early mobilisation as per institutional guidelines. Follow-up includes clinical assessments and CT scans at 1 week, 3 months, and 6 months.
Procedure: Standard Surgery Protocol
Standard burr hole drainage or craniotomy for chronic subdural hematoma, including complete evacuation of the collection and placement of a subdural drain if clinically indicated. No NTP is applied.
Other Names:
  • Standard Surgical Drainage
Experimental: Standard Surgery + Non-Thermal Plasma (NTP)
Participants randomised to this arm will receive the same standard surgical drainage procedure as described for the control arm. After evacuation of the hematoma and before wound closure, non-thermal plasma (NTP) is applied sequentially and uniformly to the surgical bed. The NTP is generated by a 13.56 MHz radiofrequency generator at 20 Watts using helium gas at 0.5 LPM. Application parameters: 60 seconds per 5 cm², nozzle-to-tissue distance of 5 mm. The plasma is applied in the following order: (1) over the exposed dura mater and any visible residual parietal membrane in the subdural space; (2) over the soft tissue layers (subcutaneous tissue) during the layered closure; and (3) over the skin incision after final closure. The total time for the NTP application is approximately 3-5 minutes. After the NTP application, wound closure is completed. All other aspects of perioperative care (antibiotics, pain management, follow-up schedule) are identical to the control arm.
Device: Non-Thermal Plasma
Standard surgical drainage as described above, followed by intraoperative application of non-thermal plasma (NTP) generated with helium gas (13.56 MHz RF generator, 20 Watts, flow 0.5 LPM). The plasma is applied sequentially and uniformly over: (i) the exposed dura mater and residual parietal membrane in the subdural space, (ii) the soft tissue layers during closure, and (iii) the skin incision after closure. Application time: approximately 60 seconds per 5 cm² area at a distance of 5 mm.
Other Names:
  • Non Thermal Plasma (NTP) Application

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence Rate of Chronic Subdural Hematoma
Time Frame: 6 months post surgery
Proportion of participants with radiological or clinical recurrence, defined as symptomatic re-accumulation requiring surgical re-intervention OR an asymptomatic volume increase ≥50% on CT scan. Unit of Measure: Percentage (%).
6 months post surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Radiological Resolution
Time Frame: From surgery to 6 months
Number of days from surgery until ≥50% reduction in hematoma volume on CT scan. Unit of Measure: Days.
From surgery to 6 months
Change in Functional Status (Modified Rankin Scale)
Time Frame: Baseline (pre-surgery) and at 6 months
Modified Rankin Scale (mRS) score ranging from 0 (no symptoms) to 6 (death). A lower score indicates better functional outcome. Unit of Measure: mRS score (0-6).
Baseline (pre-surgery) and at 6 months
Incidence of Treatment Related Adverse Events
Time Frame: From surgery to 6 months
Number of participants with local adverse events (thermal injury, wound infection, dehiscence) or neurological complications (seizure, new deficit) possibly related to NTP or the surgical procedure. Unit of Measure: Number of participants.
From surgery to 6 months
Glasgow Coma Scale (GCS) Improvement
Time Frame: Baseline (pre-surgery) and at 6 months
Change in Glasgow Coma Scale score (3-15, where 15 indicates full alertness and 3 indicates deep unconsciousness or coma). Unit of Measure: GCS points.
Baseline (pre-surgery) and at 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Benjamín Gonzalo Rodríguez Méndez

Collaborators

Centro Medico Issemym

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2026

Primary Completion (Estimated)

February 28, 2027

Study Completion (Estimated)

April 30, 2027

Study Registration Dates

First Submitted

June 16, 2026

First Submitted That Met QC Criteria

June 16, 2026

First Posted (Actual)

June 18, 2026

Study Record Updates

Last Update Posted (Actual)

June 18, 2026

Last Update Submitted That Met QC Criteria

June 16, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UEeIM.282/25

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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