Clinical Research Directory

Continuous IntraVenous Infusion of Ketamine in Terminally Ill Cancer Patients

To establish the role of ketamine in hospitalized terminally ill cancer patients with refractory cancer pain, using continuous intravenous infusion of ketamine

Esketamine Versus Crisis Response Planning Versus Enhanced Treatment as Usual for Suicide Prevention: A Pragmatic Randomized Trial in a Brazilian Municipality (SAVE)

The SAVE study will test whether a single esketamine infusion or a single Crisis Response Planning session, each added to enhanced treatment as usual, reduces future suicide-related events compared with enhanced treatment as usual alone. The study takes place in the public emergency care network of Indaiatuba, São Paulo, Brazil, and includes adolescents and adults aged 14 years or older who have attempted suicide within the previous 30 days or currently have severe suicidal thoughts with intent to act. The main questions are whether either intervention reduces suicide-related events over 12 months and whether the interventions improve suicidal thoughts, depression, anxiety, sleep, well-being, hopelessness, and quality of life. Researchers will also evaluate acceptability, feasibility, use of health services, and costs. Anticipated total enrollment is 478 participants: 10 participants in a separate pilot cohort and 468 in the main cohort used to test the study hypotheses. The main cohort will be assigned by chance, in equal numbers of 156 participants, to one of three groups: 1. Esketamine plus enhanced treatment as usual: one intravenous infusion of esketamine at 0.375 mg/kg over 40 minutes, with medical supervision and monitoring of heart rhythm, blood pressure, and oxygen levels. Participants remain under clinical observation, with discharge after 24 hours if clinically stable. 2. Crisis Response Planning plus enhanced treatment as usual: one 20-to-45-minute session with a trained clinician to develop a personalized plan covering warning signs, coping strategies, reasons for living, support contacts, and emergency resources. Participants receive a printed plan and a digital copy. 3. Enhanced treatment as usual alone: early outpatient psychiatric consultation, arranged to take place within seven days of randomization, plus lethal means safety counseling to reduce access to potentially lethal means. Both components are offered to participants in all three groups, alongside routine emergency care. The study records whether each component was delivered; booking a consultation alone does not count as receiving it. Participants will complete assessments at enrollment, 24 hours, seven days, and weeks 2, 4, 8, 16, 24, 32, 40, and 52. Blood samples will be collected at enrollment for exploratory analyses of biological factors that may be associated with treatment response. Safety monitoring and contact to identify new events will continue throughout follow-up. Participants will also use a smartphone application to answer brief questions about their mood, thoughts, and experiences during three periods of 30 consecutive days, beginning at enrollment and at calendar months 4 and 8. There will be three prompts each day: two at fixed times, 09:00 and 21:00, and one at a randomly selected time between 10:00 and 20:00, using local time in Indaiatuba. This represents 90 assessment days and 270 scheduled prompts over the study. The study team will contact participants within 24 hours of a safety alert through a dedicated study mobile phone with WhatsApp. Participants will be instructed to seek emergency care immediately when needed rather than wait for a study response. The main outcome is the time to the first qualifying event: a suicide attempt, including an attempt stopped by the person or interrupted by someone else; a psychiatric admission to prevent suicide; death by suicide; or self-injury requiring emergency department care. An external adjudicator who does not know the assigned treatment will review suspected events and determine whether they meet the study definition. Outcome assessors will also be unaware of treatment allocation. Participants who experience a qualifying event may be offered rescue treatment combining esketamine and Crisis Response Planning, depending on clinical eligibility and safety. They will remain in follow-up and in analyses according to their original randomized group. The first qualifying event will still count in the main analysis. Pilot data will be described separately and will not be included in confirmatory efficacy analyses.

Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression

Background: Major depressive disorder (MDD) is a serious mental illness that can put people at risk of self-harm and death. Many drugs are used to treat MDD, but it can take a long time for them to be effective. Researchers want to know if a faster-acting drug, (2R,6R)-hydroxynorketamine (HNK), can better treat the symptoms of MDD. Objective: To test a study drug (HNK) in people with MDD. Eligibility: People aged 18 to 70 years with MDD. They must have had a screening assessment under protocol 01-M-0254. Design: Participants will be tapered off their current MDD drugs over 2 to 5 weeks. They will stay off of the drugs for up to 2 weeks prior to starting the study medication and procedures. They will have a physical exam with blood tests. They will have tests of their heart function, mood, and thinking. They will answer questions about their symptoms. They may choose to have imaging scans and scans of their brain activity. HNK is given through a tube attached to a needle inserted into a vein. Participants will receive infusions on this schedule: They will receive 4 infusions over 2 weeks. They will stay in the clinical center overnight after each infusion or for the duration of the study. They will receive no drugs for 2 to 3 weeks. They will have 4 more infusions over 2 weeks, with overnight stays after each or for the duration of the study. One set of 4 infusions will be the HNK. The other set of 4 infusions will be a placebo. A placebo looks just like the real drug but contains no medicine. Participants will not know when they are getting the HNK or placebo. ...

Safety and Efficacy of Esketamine - Dexmedetomidine Combination Versus Dexmedetomidine Monotherapy for Hyperactive Delirium in ICU Patients on Non-Invasive Respiratory Support (SEED-NIRS Trial): Study Protocol of a Randomized Controlled Trial

This investigator-initiated, randomized, controlled, single-blind, superiority trial aims to assess the efficacy and safety of esketamine combined with dexmedetomidine for the management of agitation or delirium in intensive care unit (ICU) patients receiving non-invasive respiratory support. The primary endpoint is a clinically prioritized hierarchical composite endpoint within 28 days, including intubation or tracheostomy, delirium duration, and agitation duration.

Use of S+Ketamine During Target-Controlled Intravenous Anaesthesia After Abdominal Hysterectomy

The investigators want to investigate the effect of low dose S+ ketamine compared to placebo on cumulative morphine consumption at 24 hours in 90 women undergoing open abdominal hysterectomy with remifentanil-propofol target controlled infusion (TCI) in KK Women's and Children's Hospital. The secondary aims are to investigate the use of low dose S+ ketamine on the incidence of nausea, vomiting, pruritus (opioid side effect), sedation score and psycho mimetic assessment compared to placebo group. The investigators propose to conduct a double blinded, randomized controlled study in women undergoing open abdominal hysterectomy with remifentanil-propofol TCI. (1) Treatment Group: intravenous ketamine 0.5 mg/kg at the beginning and 0.5 mg/kg 20 minutes before extubation. (2) Control Group: intravenous normal saline (as placebo) at the beginning and 20 minutes before extubation.

Natural History of Depression, Bipolar Disorder and Suicide Risk

Mood disorders, such as depression and bipolar disorder, are difficult to treat. One reason is that there are no objective ways to measure how these disorders affect the body and respond to different treatments. In this study, researchers want to perform tests on people undergoing clinical care for mood disorders. The purpose is to understand the experience of receiving treatment for depression, bipolar disorder, and suicide risk. We also hope that this study will help us to predict which medications will improve thoughts of suicide. People 18 years or older who are receiving treatment for depression, bipolar disorder, or suicide risk may take part in this study. Participants must have also been enrolled in protocol 01-M-0254. This study will be conducted at the NIH Clinical Center in Bethesda, MD. The study typically lasts up to 12 weeks, but may last longer if a participant s treatment continues past that time. Participants will have weekly interviews and questionnaires while they are being treated for their mood disorder. Other tests are optional and include psychological testing, blood draws, sleep tests, and imaging scans. These will be done at the start and the end of research participation.

Ketamine-lidocaine Versus Ketamine-fentanyl for Induction of Anesthesia in Patients With Left Ventricular Systolic Dysfunction Undergoing Elective Coronary Artery Bypass

This study compares ketamine/fentanyl versus ketamine/lidocaine in term of their impact on cerebral perfusion during CABG. No prior data address these effects, and the goal is to identify the induction regimen that better preserves cerebral oxygenation.

Two Intravenous Doses of Ketamine in Reducing the Oculocardiac Reflex in Adult Patients Undergoing Ophthalmic Surgery

This study aims to evaluate whether a lower dose of ketamine (0.5 mg/kg IV) may be as effective as a higher dose (0.75 mg/kg IV) in reducing oculocardiac reflex (OCR) incidence in adult patients undergoing ophthalmic surgery.

Biomarker-Guided Antidepressant Selection

Depression is one of the leading causes of disability worldwide. Common treatments like antidepressant medications and talk therapy work well for some people, but many others do not improve, even after trying multiple treatments. This study will investigate two alternative treatment options for people whose depression has not responded to standard treatments: repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, and ketamine, a fast-acting medication. It can be difficult to decide between these interventions in clinical practice, and selecting between them often comes down to patient preference and trial and error. This study is working to optimize the selection approach: using biological and behavioral markers to match each person to identify biomarkers that may predict response to rTMS or ketamine. Investigators believe that differences in how individuals respond to rTMS versus ketamine are partly explained by differences in how their brains are organized, and that these differences can be measured and used to guide intervention decisions. This is an early-stage pilot study designed to test whether this biomarker-based approach is practical and acceptable to patients. Investigators will evaluate how well a combination of brain imaging and clinical data can predict, at the individual level, who is likely to respond to rTMS versus ketamine. The ultimate goal is to develop a reliable, scalable tool that helps clinicians make faster and more informed intervention decisions, reducing the time people with treatment-resistant depression spend searching for an antidepressant that works.

Nebulized Ketamine for the Treatment of Major Depressive Disorder

This is a double-blind active placebo controlled clinical trial for individuals with moderate to severe depression. The purpose of this study is to assess if nebulized ketamine can reduce depressive symptoms.

Induction Agent Choice With Early Mortality and Prognostic Outcomes in Critically Ill Patients

The aim of this retrospective cohort study is to compare the safety and efficacy of induction agents for tracheal intubation in critically ill adult patients.

Postoperative Opioid Consumption in Gastric Sleeve Surgery

The study aimed to compare balanced anesthesia protocols using only opioids as analgesics during induction in gastric sleeve surgery with protocols using opioids and ketamine together in terms of anesthesia management, opioid side effects, and postoperative analgesia.

Intraoperative Ketamine for Chronic Postoperative Pain After Open-Heart Surgery

The goal of this interventional study is to determine whether a single intraoperative IV dose of ketamine can reduce postoperative chronic and acute pain and postoperative opioid requirements in adult patients undergoing open-heart surgery under general anesthesia. The main questions it aims to answer are: Primary outcome: Does a single-dose intraoperative IV ketamine reduce the presence and severity of pain at 3 and 6 months after surgery ? Secondary outcomes: Does it reduce acute postoperative pain scores, opioid consumption, and other recovery-related outcomes in the early postoperative period ? Researchers will compare a single-dose IV ketamine arm to a placebo arm to see if ketamine decreases chronic pain incidence at 3 and 6 months and improves acute pain/opioid-related outcomes. Participants will: Be randomized to receive either a single IV bolus of ketamine or placebo during surgery. Undergo standard general anesthesia and open cardiac surgery per protocol. Have postoperative pain assessed using Numeric Rating Scale (NRS) at extubation, 0, 3, 6, 12, 24, and 48 hours. Have opioid and additional analgesic use recorded, time to first rescue analgesic noted, and ICU/hospital length of stay tracked. Be evaluated for ICU delirium (CAM-ICU) and complete Quality of Recovery-15, Brief Pain Inventory-Short Form, and Pain Self-Efficacy questionnaires. Be followed up at 3 and 6 months for assessment of chronic postoperative pain.

Role of Opioid Free Anaesthesia in Elderly Patients Undergoing Elective Coronary Artery Bypass Graft Surgeries With Cardiopulmonary Bypass in Enhanced Recovery After Surgeries

The introduction of synthetic opioids in 1960 to general anesthesia together with sedative hypnotics and muscle relaxants allowed the appearance of the concept of multimodal balanced anesthesia. Although they help in achieving hemodynamic stability during anesthesia of open heart surgeries, their administration consequences are neither scarce nor benign to the patient. Perioperative opioids are associated with increased incidence of respiratory depression, prolonged mechanical ventilation, nausea and vomiting, prolonged sedation, Postoperative ileus (POI), urine retention, Postoperative cognitive dysfunction (POCD), immune depression and hyperalgesia (Beloeil et al., 2018). Coronary artery bypass graft surgery with cardiopulmonary bypass (CPB) is particularly vulnerable to the above-mentioned complications. Indeed, some of the side effects of this surgery overlap with the adverse effects of opioids. Postoperative pulmonary complications are observed in up to 50% of patients (Fisscher et al., 2022) and POCD or delirium in 4-54% according to studies (Bhushan et al., 2021). Whereas major gastrointestinal complications are estimated to occur in around 3% of patients, essentially acute pancreatitis, postoperative ileus (Marsoner et al., 2019). Opioid-free anesthesia (OFA) strategies have emerged to avoid intraoperative opioid use. It is based on the fact that a sympathetic reaction evidenced by hemodynamic changes in an anesthetised patient does not systematically reflect pain. In addition, a sleeping patient will not recall pain, while hormonal stress and sympathetic and inflammatory reactions can be controlled by therapeutic classes

Anesthesia Techniques, Neuroprotection and Surgical Field in FESS Under Controlled Hypotension

This prospective, randomized controlled trial investigates the effect of four different anesthetic maintenance techniques on surgical field conditions, hemodynamic stability, and neuroprotection during functional endoscopic sinus surgery (FESS) performed under controlled hypotension. Patients are randomly assigned to receive either total intravenous anesthesia with propofol-remifentanil, propofol-remifentanil with adjunct ketamine and magnesium, sevoflurane-remifentanil, or sevoflurane-remifentanil with adjunct ketamine and magnesium. Primary outcomes include serum biomarkers of neuronal injury (S100B and neuron-specific enolase, NSE) measured perioperatively, as well as surgical field visibility and intraoperative bleeding scores. Secondary outcomes include recovery profile and postoperative pain.

Intraoperative Combination of Ketamine and Magnesium Sulfate Infusions on Postoperative Analgesia in Open Rhinoplasty

The study aims to evaluate the effectiveness of intraoperative combination of ketamine and magnesium sulfate infusions on postoperative analgesia in patients undergoing open rhinoplasty.

ECT with Ketamine Anesthesia Vs High Intensity Ketamine with ECT Rescue for Treatment-Resistant Depression

To determine if an high intensity ketamine with ECT rescue (HIKER) approach for treatment resistant depression will: 1) reduce patient suffering by hastening disease remission, 2) have fewer side effects, 3) reduce the need for ECT, and 4) be preferred by most patients. Half of participants will be randomized to the HIKER arm and receive high intensity ketamine treatment for eight consecutive days, and the other half will be assigned to the ECT with ketamine anesthesia (EAST) arm and receive 8 ECT treatments (2-3 treatment/week)

Effect of Low-dose Esketamine on Maternal Depression at 3 Years After Childbirth

Postpartum depression refers to the depression after childbirth, which is a common mental disorder in women. The pathogenesis of postpartum depression is not fully understood, and may be related to a variety of factors. Prenatal depression is an important risk factor for postpartum depression. Our recent multicenter randomized controlled trial, "Effect of Low-dose esketamine on the incidence of postpartum depression in women with prenatal depression", explored the effect of immediate postpartum intravenous infusion of low-dose esketamine on the incidence of postpartum depression in women with prenatal depression. The preliminary results showed that it reduced the incidence of postpartum depression at 42 days. Since there were no studies on the effect of intravenous esketamine infusion after delivery on long-term postpartum depression, this study is a long-term follow-up of the previous randomized trial. We aim to explore the effect of low-dose intravenous esketamine after delivery on the incidence of 2-year maternal depression after delivery in women with prenatal depressive symptoms.

Safety and Efficacy of Esketamine Combined With Dexmedetomidine for Sedation of Mechanically Ventilated Patients

A prospective, randomized controlled study was conducted to compare the effects of esketamine combined with dexmedetomidine in the sedation and analgesia treatment of mechanically ventilated patients in the ICU on the time to awaken, time to extubation, time to mechanical ventilation, time in the ICU, and on delirium.