Suicide is a major global health issue, with over 700,000 deaths in 2019 [1]. In India, hanging accounts for 58.2% of suicides, making it the leading cause [2]. Fatal hanging causes immediate death, while nonfatal (or near-hanging) cases survive the attempt and manage to reach the hospital [3]. Patients surviving near-hanging often have varying degrees of injury to vital neck structures, often requiring intensive care. Key management focuses on airway protection, aspiration pneumonia, pulmonary complications, and cervical spine injury; preventing secondary brain injury caused by reperfusion after the release of the obstruction; and treating cerebral edema and hypoxic damage [4-8]. Neurological injury in the form of cerebral edema critically affects long-term outcomes [4,7,8].

Brain injury caused by near-hanging is due to cerebral hypoxia resulting from airway obstruction, compression of the carotid arteries, compression of the jugular veins, or a combination of these mechanisms. Secondary brain injury due to reperfusion further worsens brain damage [5,9]. The damage occurs through several processes, including inflammation, oxidative stress, damage to brain cells, and disruption of the blood-brain barrier, causing cerebral edema. Cerebral edema can further increase once compression is relieved and blood flow returns [10-12]. This cerebral edema may represent a therapeutic target, as it is a potentially reversible component of brain injury. This edema can be due to cytotoxic edema (cellular energy failure leading to intracellular water accumulation) or vasogenic edema (leakage of fluid into brain tissue after damage to the blood-brain barrier), and both types may occur together [10-13]. Although direct evidence in near-hanging is limited, these processes are well described in hypoxic brain injury, traumatic brain injury, ischemic stroke, high-altitude cerebral edema (HACE), and other neurocritical illnesses [14-17].

Corticosteroids, such as dexamethasone, are favored for their blood-brain barrier penetration and reduce vasogenic cerebral edema by stabilizing the blood-brain barrier, reducing endothelial permeability, and suppressing inflammation [14,18]. They are effective in conditions such as brain tumors and bacterial meningitis, but their role in acute brain injury remains doubtful. The Medical Research Council CRASH (Corticosteroid Randomization after Significant Head Injury) trial demonstrated increased mortality in traumatic brain injury with the use of corticosteroids [19].

Corticosteroids are used to treat cerebral edema in near-hanging patients with altered sensorium, despite limited evidence [20]. Their proven role in HACE, involving hypoxia- and inflammation-driven edema, prompts extrapolation to hanging cases [15-17]. As the pathophysiology of hanging-induced cerebral edema is poorly understood, this analogy is theoretical.

A retrospective study from a South Indian tertiary care center admitted 323 near-hanging patients over 5 years, most of whom were young-or middle-aged men. Steroids were given to 68% (219/323) of patients, mainly dexamethasone (200/219) [17]. Among patients with Glasgow Coma Scale (GCS) ≤13 cases (n=201), steroid recipients (n=160, 80%) had 77% good outcomes vs 90% in nonrecipients (n=41, 20%), but selection bias favored administering steroids to sicker patients, and steroid dosing and duration varied. No established guidelines exist for managing near-hanging, including steroid use, which contributes to wide practice variations [21].

At present, the use of corticosteroids in near-hanging patients with impaired consciousness is inconsistent and guided largely by individual clinicians’ preferences and assumptions about shared pathogenesis with other traumatic brain injuries and similar conditions, rather than by evidence-based recommendations. There are no established guidelines or randomized controlled trials addressing this therapeutic dilemma. This lack of clarity creates genuine clinical equipoise regarding the role of steroids in managing cerebral edema following near-hanging, underscoring the urgent need for high-quality prospective evidence.

This study aims to systematically evaluate the efficacy of steroid therapy in near-hanging patients with altered sensorium. The findings are expected to generate evidence that may guide clinical decision-making and contribute to the development of standardized treatment recommendations.

The primary objective of this study is to evaluate the efficacy of intravenous dexamethasone, compared with placebo, in achieving a good neurological outcome (Glasgow Outcome Scale [GOS] 4‐5) at day 28 in patients presenting with near-hanging with altered sensorium. Secondary objectives are to assess neurological outcomes at hospital discharge, compare the length of hospital stay, and compare the incidence of in-hospital complications between the dexamethasone and placebo groups.

The CHANGING trial (Corticosteroids in HANGING) is a multicenter, double-blind, randomized, placebo-controlled clinical trial designed to evaluate whether intravenous dexamethasone improves neurological outcomes in patients presenting with near-hanging. This protocol has been designed in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 statement (Checklist 1) to ensure robust and transparent reporting of the study methodology [22,23]. The flow chart depicting the various stages of the study is shown in Figure 1.

The primary site, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, is the coordinating site. The principal investigator and coinvestigators at the primary site were involved in protocol development and securing funding for this trial from the Indian Council of Medical Research (ICMR), New Delhi. The primary site will conduct training, data monitoring, randomization, and quality control for the other 2 sites, Indira Gandhi Medical College and Research Institute (IGMCRI), Puducherry, and Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh. All 3 sites will competitively recruit consecutive patients admitted with near-hanging. All sites are responsible for following the protocol and ensuring the quality of the data collected.

This trial will be conducted in the Departments of Medicine and Emergency Medicine at 3 tertiary care centers in India: JIPMER, Puducherry; IGMCRI, Puducherry; and PGIMER, Chandigarh.

Patients with near-hanging presenting to the emergency medicine departments of 3 study centers—JIPMER, Puducherry (JI); IGMCRI, Puducherry (IG); and PGIMER, Chandigarh (PG)—will be the study participants.

The inclusion and exclusion criteria for the study participants are shown in Textbox 1.

Central randomization will be conducted at the coordinating center. Participants will be randomly allocated in a 1:1 ratio to receive either intravenous dexamethasone or placebo using a computer-generated randomization sequence. Variable block sizes of 4 and 6 will be used, with stratification based on baseline GCS score (≤8 and >8) to ensure balance between the treatment groups. Allocation concealment will be ensured using the Sequentially Numbered Opaque Sealed Envelopes method.

The study medications (dexamethasone or placebo) are prepared in identical-looking vials and labeled with a 5-character alphanumeric code using a randomly generated sequence, as shown in Figure 2. They are securely packed in designated boxes for each site. The random sequence used for labeling the study medications is stored in a password-protected Microsoft Excel sheet, accessible only to an unblinded investigator at the primary site to ensure confidentiality and maintain blinding throughout the study.

A designated coinvestigator who is the only unblinded person other than the study statistician at the primary site will assume responsibility for crucial aspects of randomization, allocation concealment, and maintenance of the blinding process. All other staff (investigators, nurses, outcome assessors, and research team) and participants remain blinded to treatment assignments throughout the trial. After eligibility confirmation and written consent, the site team contacts the unblinded coinvestigator at the coordinating center. This investigator reconfirms eligibility and consent, performs randomization, and shares only the study drug label number supplied to each site, never revealing the actual treatment allocation.

Data will be collected by trained staff at each center using standardized case report form (CRF) booklets and entered into a password-protected REDCap (Vanderbilt University) electronic database. As each participant is given a unique enrollment ID, the data will be collected in a deidentified manner. Data will include demographics, medical history, comorbidities, details of the hanging event, and findings from a complete physical examination. Baseline investigations will comprise a complete hemogram, renal and liver function tests, serum electrolytes, random blood sugar, chest X-ray, ECG, and arterial blood gas analysis with PaO₂ and PaO₂/FiO₂ (PF) ratio. NCCT of the head and cervical spine will be performed when clinically indicated to evaluate for cerebral edema or cervical spine injury.

During the first 5 days of hospitalization, patients will undergo daily monitoring of physiological status, neurological function, organ dysfunction, and treatment variables. Neurological status will be assessed using the GCS at admission, every 6 hours on day 1, and every 24 hours thereafter, with adjustments for sedation. Hemodynamic parameters, including heart rate, mean arterial pressure, and the requirement for vasoactive agents, will be recorded, along with respiratory parameters such as respiratory rate, PF ratio, and ventilatory status. The need for organ support, including mechanical ventilation, inotropes, and sedatives, as well as details of antibiotic therapy, will be documented. Sequential Organ Failure Assessment (SOFA) scores will be calculated using platelet count, serum creatinine, bilirubin, mean arterial pressure or vasopressor requirement, PF ratio, and GCS at predefined time points.

Laboratory monitoring will be conducted to assess disease progression and potential steroid-related adverse effects. On days 2 and 3, a complete hemogram, blood glucose levels, and serum potassium will be measured to screen for complications such as infection, hyperglycemia, and hypokalemia. If steroid therapy is continued beyond day 3, similar laboratory monitoring will be repeated on days 4 and 5. SOFA scores will be recalculated on days 3 and 5. This monitoring schedule is shown in Table 2.

Patients will be closely observed for adverse events (AEs) throughout the study period, including nosocomial infections, significant gastrointestinal bleeding requiring transfusion, hyperglycemia (random blood sugar >180 mg/dL), electrolyte abnormalities, and cardiac or respiratory arrest requiring cardiopulmonary resuscitation. Protocol deviations, reasons for withdrawal, and final hospital outcomes will be documented. All participants will be followed up for 28 days, and for those discharged earlier, follow-up will be completed either through hospital visits or telephone contact if they are unable to visit the hospital. A screening log will be maintained at each participating center to document all patients admitted after a near-hanging.

AEs will continue to be monitored and documented. If participants continue to receive steroids for more than 5 days, this will be noted. All concomitant medications, including those given empirically to treat possible alternative causes of severe illness, will be recorded.

This study is prospective, so we do not expect any missing data. If we are unable to follow up and obtain outcome data, we will use imputation to fill in the missing data.

The outcome assessment will include the GOS at discharge (shown in Table 3) [24]. We will also assess the duration of study medication, whether full sensorium is achieved during hospitalization, and the time taken to achieve full sensorium (defined as a GCS score of 15 maintained for more than 24 h). Additional outcomes will include the duration of hospital stay and intensive care unit stay, the need for ventilatory support, including its duration and type, and the requirement for vasoactive support and its duration, if applicable. All AEs, as defined in the study protocol, will be documented. For participants who do not complete the study, the reasons for noncompletion will be recorded in detail.

The patient will be called for a follow-up on day 28 to assess GOS. The outcome will be assessed by the study staff who are blinded to the treatment allocation. If the patient cannot attend in person, GOS will be ascertained by telephone or video call. A standardized, structured interview process will be followed during the outcome assessment. Participants who die before day 28 will be assigned a GOS of 1 and will be included in the primary outcome analysis.

The end of the study is defined as the time when the last participant has either completed the 28-day follow-up or discontinued the study early.

Each participant is free to discontinue participation or withdraw their consent at any time. If volunteered by the participant, the reason for discontinuation or withdrawal of consent will be recorded in the CRF. If a patient requests to stop participating, the investigator should ask if the patient would be willing to stop the treatment but continue follow-up. If they do not agree to this, the investigator should ask for their permission to contact them to determine their status on day 28.

Expected adverse effects of the intervention drug (dexamethasone) include hyperglycemia, hypokalemia, and infection. These adverse effects will be managed according to standard guidelines. If these adverse effects are not successfully treated, the participant will be withdrawn from the study, and the adverse effects will be managed.

This trial has been registered with the Clinical Trials Registry India (CTRI/2025/02/081343) on February 25, 2025. Patient recruitment commenced on October 3, 2025.

Given the interventional nature of this trial, an independent Data and Safety Monitoring Board (DSMB) has been constituted in accordance with JIPMER’s DSMB guidelines to oversee participant safety and trial conduct. A DSMB charter was developed prior to trial initiation. The charter details the composition of the committee, minimum quorum requirements, frequency of meetings, the structure of meetings (open and closed sessions), and the procedures for documentation, communication, and reporting of recommendations.

The DSMB comprises 3 independent members: one expert from each of emergency medicine, internal medicine, and biostatistics. A quorum of 2 members is required for DSMB meetings. The study statistician will be responsible for presenting the interim efficacy analyses, and a consolidated summary of all AEs and SAEs will be submitted for DSMB review. The DSMB will periodically review accumulated safety and efficacy data, including a planned interim review after 50% enrollment in each treatment arm. Based on its evaluation, the DSMB may recommend continuation of the study without modification, protocol modification, or early termination of the trial. All DSMB recommendations will be formally communicated to the principal investigator, who will subsequently report them to the Institutional Ethics Committee.

An interim analysis will be conducted after enrollment of 50% of the planned sample size. The Haybittle-Peto stopping rule will be applied, with statistical significance for early termination defined as a P <.002 at the interim analysis stage. However, the final analysis will retain a 2-sided α level of .05.

The coordinating center will monitor the study and ensure compliance with the protocol, Good Clinical Practice guidelines, and relevant regulatory requirements. A checklist has been created to ensure the readiness of each site to start patient recruitment. A site initiation meeting will be held via an online platform, and study investigators from the primary center will conduct a site visit to ensure that sites are equipped and able to run the trial. In addition, the lead center will conduct regular online meetings to ensure compliance with the study protocol and the integrity of the study data.

The results of the trial will be disseminated through publication in a peer-reviewed journal so that the scientific community can use the conclusions of this study to manage patients better. Authorship will be based on contributions to the study. Following completion of the study, the principal investigator will have access to the final dataset.

The sample size was calculated to detect a clinically meaningful difference in the proportion of patients achieving a good neurological outcome (GOS 4‐5) at day 28 between the dexamethasone and placebo groups. In our previous retrospective study, approximately 75% of near-hanging patients with altered sensorium who received steroids achieved a good neurological outcome [17]. Using these data, the expected event rate in the intervention group was assumed to be 75% while a favorable neurological outcome rate of 55% was assumed in the placebo group, corresponding to an absolute treatment effect of 20%.

The sample size for this superiority trial with a binary outcome was calculated using a 2-sided α of 0.05% and 80% statistical power. Sample size estimation was performed using the Sealed Envelope online sample size calculator for binary superiority trials [27]. The calculated sample size was 86 participants per treatment arm. To account for an anticipated 10% attrition rate due to loss to follow-up or protocol deviations, the sample size was inflated to 96 participants per arm, resulting in a total sample size of 192 participants.

The effect size was chosen as a pragmatic compromise between clinical relevance and study feasibility. Near-hanging with altered sensorium is an uncommon emergency presentation, and, based on patient admissions at the 3 study sites, 190 to 200 eligible patients were expected to be recruited during the planned study period. For detecting a smaller treatment effect, we will require a substantially larger sample size that will not be feasible within the available study period and funding. Despite this, an absolute improvement of 20% in favorable neurological outcomes was considered clinically important because such a benefit would be expected to substantially influence clinical practice, whereas failure to demonstrate a benefit of this magnitude would provide evidence against the routine empirical use of corticosteroids in this population.

Several amendments were made to the study protocol to improve feasibility, clarity, and participant safety. The current version of the protocol is version 1.5, dated July 1, 2025. The inclusion window was extended from 24 hours to 48 hours following a hanging attempt, as several otherwise eligible patients were referred from nearby districts and presented beyond the original 24-hour period, leading to the loss of potential participants. This change was implemented to enhance recruitment, given the relatively low number of hanging cases.

The exclusion criterion related to corticosteroid use was corrected to address a typographical error: the intended exclusion dose was clarified as 20 mg of dexamethasone or an equivalent corticosteroid dose, rather than 24 mg. Additional exclusion criteria were introduced to explicitly exclude patients with a definite indication for, or contraindication to, steroid therapy, and to clearly state the exclusion of patients who did not provide informed consent.

Amendments were also made to the criteria for discontinuation of the study drug. While the originally planned duration of study drug administration was 3 to 5 days, a predefined tapering or early discontinuation strategy was introduced for patients who achieved rapid neurological recovery (GCS score of 15/15), particularly if this occurred by day 1, to minimize unnecessary drug exposure and ensure patient safety. Furthermore, mandatory permanent discontinuation of the study drug was specified for participants who developed a definite indication for or contraindication to steroid therapy during the trial period. All amendments were made to enhance patient safety, improve protocol clarity, and address issues encountered during recruitment.

The hypoxic-ischemic brain injury seen in near-hanging is associated with substantial mortality and long-term neurological disability despite advances in critical care [5,7]. The secondary brain injury determines the neurological outcome despite prompt resuscitation. Jugular venous obstruction results in flow stagnation, leading to cerebral hypoxia, which may be the initial event in hanging. Excessive cerebral perfusion of an already hypoxic brain following relief of obstruction may also contribute to cerebral edema [5,21]. Currently, there is no guideline-directed therapy for improving neurological recovery in these patients, and the management is only supportive [21].

The pathophysiology of cerebral edema in near-hanging is poorly understood. The following mechanism is proposed for hypoxia-induced cerebral edema at high altitudes and in traumatic brain injury. Hypoxia at altitude elicits neuro-hormonal (VEGF, nitric oxide, reactive cytokines, and free radicals) and hemodynamic responses, resulting in hypoxia-induced cerebral vasodilation leading to over perfusion of microvascular cerebral beds. This leads to intracranial hypertension with elevated capillary pressure and capillary leakage. The disruption of the blood-brain barrier from these stressors leads to subsequent vasogenic cerebral edema. Another theory is that hypoxia induces free radical formation, causing damage or failure of the Na+/K+ATPase pump with resultant astrocyte swelling from osmotic-oxidative stress and subsequent cytotoxic edema [29]. Similarly, hypoxia can cause cerebral edema in hanging patients. Steroids are indicated to treat vasogenic cerebral edema, whereas osmotic agents such as mannitol and hypertonic saline are preferred for the treatment of cytotoxic edema. The rationale for using dexamethasone in hanging-related cerebral edema is that it has demonstrated clinical benefit in conditions characterized predominantly by vasogenic cerebral edema, including bacterial meningitis and brain tumors [30].

There is very limited evidence for the use of corticosteroid therapy in near-hanging. The existing literature is predominantly retrospective and comprises narrative reviews with several methodological limitations [8,18,31]. Our previous retrospective study demonstrated frequent empirical use of corticosteroid therapy in routine clinical practice but could not establish treatment efficacy because of its observational design [17]. No randomized controlled trials are currently available on steroid therapy specifically for near-hanging patients. However, there are studies available on steroid therapy for traumatic brain injury that closely resemble the type of brain injury seen in near-hanging cases. The MRC CRASH trial studied corticosteroids in patients with head injury, finding a higher death rate in those given corticosteroids (25.7%) compared with placebo (22.3%). This suggests that corticosteroids should not be used routinely to treat head injuries [19].

A narrative review by Kannamani et al [21] on near-hanging described head-end elevation, sedation, maintaining normocapnia (PaCO₂ of 30‐35 mm Hg), and osmotic diuretics (hypertonic saline, mannitol) as management for cerebral edema and did not include steroid therapy in the management. A short review on steroid therapy in near-hanging patients reported that there is no evidence for or against the use of steroids in this situation [32].

Our CHANGING trial has been designed to address this evidence gap through a multicenter, randomized, double-blind, and placebo-controlled design. Random allocation and blinding of participants, treating clinicians, and outcome assessors are expected to minimize selection and assessment bias [22,28]. The study is conducted in 3 different tertiary care hospitals, which will improve external validity by including patients across diverse intensive care settings. To enhance the reliability of the study findings, the study follows a standardized treatment protocol, predefined neurological outcome, and systematic AE reporting [22].

Our trial uses patient-centered functional outcome as the primary endpoint. The assessment of neurological recovery using the Glasgow Outcome Scale at day 28 reflects clinically meaningful recovery rather than just a physiological improvement and has been widely used in studies of traumatic brain injury [24,33]. Simultaneous assessment of AEs will aid in balancing potential neurological benefits against complications related to corticosteroids, including hyperglycemia, secondary infections, hypokalemia, and gastrointestinal bleeding [34].

There are a few anticipated limitations to consider; this trial is being conducted at 3 tertiary care centers in India, which may limit the generalizability of the findings to other public and private hospitals or to international populations. The sample size calculation assumed a 20% absolute difference between the treatment groups, which may be considered relatively high. This assumption was made to ensure feasibility within the constraints of the 3-year study period, available funding, and the limited number of near-hanging cases, and it represents a pragmatic compromise between feasibility and statistical power. Short-term follow-up (28 d) is also a limitation.

The CHANGING trial seeks to address a major evidence gap in the management of near-hanging patients with altered consciousness, a population in whom corticosteroids are widely used despite limited supporting data. Through a rigorous multicenter, double-blind, placebo-controlled design, this study aims to determine whether dexamethasone improves neurological outcomes and safety. The results are expected to provide definitive evidence to guide clinical practice and inform future guidelines for managing near-hanging-associated cerebral injury.