NCT04490005: ORANGE

Outcome pRognostication of Acute Brain Injury With the NeuroloGical Pupil indEx

Completed Last updated 25 January 2023

What this trial tests

trial testing pupillometry in Acute Brain Injury in 118 participants. Completed in 3 May 2022.

Timeline

2 November 2020

Primary endpoint
2 April 2022

3 May 2022

Quick facts

Lead sponsor	University of Milano Bicocca
Status	Completed
Study type	OBSERVATIONAL
Enrollment	118
Start date	2 November 2020
Primary completion	2 April 2022
Estimated completion	3 May 2022
Sites	14 locations across France, Italy, Belgium, Germany, Norway, Switzerland, United States, Spain

Drugs / interventions tested

• pupillometry

Conditions studied

• Acute Brain Injury — all drugs for Acute Brain Injury →
• Pupillary Reflex Impaired — all drugs for Pupillary Reflex Impaired →

Sponsor

University of Milano Bicocca

Who can join

18 and older, any sex, with Acute Brain Injury or Pupillary Reflex Impaired. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The use of quantitative, automated, infrared technology for pupillary examination has long been used in ophthalmology and anesthesiology research. Its interest in neurocritical care has progressively grown, in parallel with the advancements in device technology. In this regard, the use of the noninvasive NPi®-200 pupillometer (Neuroptics, Laguna Hills, California, USA) allows the measurement of a series of dynamic pupillary variables (including the percentage pupillary constriction, latency, constriction velocity, and dilation velocity), which can be integrated into an algorithm, to compute the Neurological Pupil index (NPi). The NPi is a proprietary scalar index with values between 0 and 5 (with a 0.1 decimal precision), an NPi value \< 3 indicating an abnormal pupillary reactivity. Importantly, the NPi is not influenced by sedation-analgesia, at the doses used in neurocritical care practice, and by mild hypothermia.

Preliminary single-center data recently demonstrated that abnormal NPi is associated with worse outcome in patients with traumatic and hemorrhagic ABI, and can be a useful adjunct for ICP monitoring and therapy. There is currently a great need for quantitative tools to predict early prognostication in ABI patients, and the NPi appears of potential great value.

We hypothesize that:

1. Abnormal NPi (defined as NPi \<3) are strongly predictive of poor GOS-E (1-4) at 6 months after the acute event.
2. NPi=0 is strongly predictive of mortality (GOS 1).
3. Abnormal NPi is predictive of a higher ICP 20 index (number of end-hourly measures of ICP \>20 mm Hg divided by the total number of measurements, multiplied by 100) and a greater burden of interventions needed to control ICP (measured by the Therapy Intensity Level scale for ICP management, Therapy Intensity Level (TIL) 4).

Methods This international multicentre prospective observational study aims to recruit \>400 patients admitted to intensive care units.

Duration of the study 18 months, including 12-month of recruitment based on 60 patients/centre plus 6 months GOS-E follow-up.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. The Neurological Pupil index for outcome prognostication in people with acute brain injury (ORANGE): a prospective, observational, multicentre cohort study.
   Oddo M, Taccone FS, Petrosino M, Badenes R, et al · · 2023 · cited 71× · PMID 37652068 · DOI 10.1016/s1474-4422(23)00271-5
2. Outcome Prognostication of Acute Brain Injury using the Neurological Pupil Index (ORANGE) study: protocol for a prospective, observational, multicentre, international cohort study.
   Oddo M, Taccone F, Galimberti S, Rebora P, et al · · 2021 · cited 19× · PMID 33980528 · DOI 10.1136/bmjopen-2020-046948
3. Neurological Pupil Index and Intracranial Hypertension in Patients With Acute Brain Injury: A Secondary Analysis of the ORANGE Study.
   Petrosino M, Gouvêa Bogossian E, Rebora P, Galimberti S, et al · · 2025 · cited 15× · PMID 39652324 · DOI 10.1001/jamaneurol.2024.4189