International Journal of Clinical Trials

Multimodal analgesia strategies for optimal postoperative pain relief

Shehla Ashraf — 2025-04-28

This narrative review assesses the effectiveness of multimodal analgesia protocols (MAPs) in managing postoperative pain and reducing opioid consumption, focusing on their safety, efficacy, and broader applicability in clinical practice. Recent studies highlight that MAPs, which combine pharmacological and non-pharmacological methods, significantly reduce postoperative pain intensity and opioid use compared to traditional opioid-centric approaches, without increasing adverse events such as nausea and respiratory depression. The inclusion of regional anaesthesia, nonsteroidal anti-inflammatory drugs (NSAIDs), and nerve blocks has shown to enhance recovery, minimize complications, and improve patient outcomes. Specific combinations of medications like ketamine, acetaminophen, and dexamethasone have proven effective in different surgical settings, underscoring the versatility of MAPs. By leveraging the synergistic effects of various pain relief modalities, MAPs optimize pain control while reducing opioid-related risks, offering a promising strategy for improving recovery outcomes. This review emphasizes the need for broader adoption of MAPs and calls for further research to refine these protocols for long-term advancements in surgical care and patient experiences.

The face of Sagliker’s syndrome in maxillofacial aspect: a brief review

Runal Bansod — 2025-04-28

In the world of nephrology, Sagliker syndrome is a unique rarity whose mechanism of occurrence is still not known. A rare bone disease characterized by secondary hyperparathyroidism in patients with chronic renal failure, caused by improper treatment in the early stages of the disease with retention of phosphorus, vitamin D deficiency, and disturbed calcium-phosphorus metabolism, which result in increased parathyroid hormone levels. Patients present with short stature, severe changes of the skull and jaws as well as other skeletal deformities, dental anomalies, ''brown tumors'' in the mouth, hearing loss, and neuropsychiatric disorders. This review briefly covers the maxillofacial aspect and core of Sagliker’s syndrome.

A series of choroidal melanoma in young patients: insights from a tertiary care facility

Sonali Vinay Kumar — 2025-04-28

Choroidal melanoma is rare in young individuals and often presents at a later stage due to low clinical suspicion. This case series describes a group of young patients, all under the age of 30 years, who presented with advanced choroidal melanoma requiring enucleation. A prospective observational study was conducted from January 2019 to December 2023 at a tertiary care center. Twelve young patients diagnosed with choroidal melanoma were assessed. Patient’s demography, clinical presentation, tumor characteristics and histopathological findings were noted. Histopathologically tumors were classified as epithelioid, mixed and spindle cell type. The treatment protocol was devised based on the size, extent of the lesion and any involvement of systemic system. There were 10 females and 02 males. The mean age of patients in the current study was 23±3.5 years. Right eye was involved in 05 patients and left eye was involved in 07 patients. All patients had advanced choroidal melanoma at the time of presentation at our center. The mean basal diameter of the tumor was 21±2 mm and thickness were 11±1.5 mm. Primary enucleation with implant was the most common treatment modality in all patients. Epithelioid cell type choroidal melanoma was the commonest histology pattern was found in the current study. No mortality or death occurred at the end of 02 years follow-up in any patient. This series highlights the aggressive nature of choroidal melanoma in young individuals when diagnosed at an advanced stage. It emphasizes the importance of early clinical suspicion, timely referral, and appropriate imaging in any atypical choroidal lesion in the young population.

Preventing post-operative seizures in chronic subdural hematoma surgery: role of antiepileptic drugs

M. Omar Faruk — 2025-04-28

Background: Seizures are a known complication of chronic subdural hematoma (CSDH) and its surgical treatment. While anti-epileptic drugs (AEDs) are often used prophylactically, there is limited evidence of their efficacy in the Bangladeshi population. This study was planned to determine the role of AEDs in preventing postoperative seizures in patients undergoing surgical treatment for CSDH.

Methods: This quasi-experimental study was conducted on 100 patients with CSDH undergoing Burr hole evacuation in the Department of Neuro Surgery at Bangabandhu Sheikh Mujib Medical University (BSMMU) and Dhaka Medical College Hospital (DMCH) from March 2015 to February 2017. Patients were divided into a study group (n=50, no antiepileptics) and a control group (n=50, given Phenobarbitone). Standard postoperative care was provided, with follow-ups on the 1st postoperative day, at discharge (7-10 days), and at 4 weeks. The control group continued Phenobarbitone post-discharge. Seizure occurrence was monitored throughout follow-ups to evaluate the drug's effectiveness in preventing postoperative seizures.

Results: The study population was predominantly male (71.0%), with most participants aged 51-60 years. At baseline, both groups were similar in terms of demography, clinical presentation, and level of consciousness. No preoperative seizure was noted among the study participants. Postoperative seizure incidence was 4.0% among the study group, whereas no one in the control group had developed a seizure. However, no significant difference in postoperative seizure proportion was found between the two groups.

Conclusions: Routine prophylactic use of antiepileptic adds no benefits in postoperative seizure prevention in CSDH patients.

AIM HD-CKD study: assessment of the efficacy and safety of ferric carboxymaltose in iron deficiency anemia management in haemodialysis patients with chronic kidney disease

Umesh Khanna — 2025-04-28

Background: Iron deficiency anemia (IDA) is a common complication in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). Intravenous (IV) iron supplementation is essential for managing IDA in these patients, and ferric carboxymaltose (FCM) has emerged as a promising treatment option.

Methods: This multicentric, retrospective observational study was conducted from April to August 2023, involving 52 adult HD-CKD patients with IDA in India. During dialysis sessions, 48 patients received 4 weekly doses of 100 mg FCM IV push, while 4 patients received 3 doses. Hematological parameters, including haemoglobin (Hb), serum ferritin, transferrin saturation (TSAT), C-reactive protein (CRP), and estimated glomerular filtration rate (eGFR), were measured at baseline and after the final FCM dose. The primary outcome was the change in Hb levels, with secondary outcomes focusing on changes in ferritin, TSAT, CRP, eGFR, and the safety profile of FCM.

Results: Following FCM administration, a significant increase was observed in Hb levels (+0.69 g/dl, p<0.001), serum ferritin (+8.61 ng/ml, p=0.003), and TSAT (+3.69%, p<0.001). CRP levels showed a slight, non-significant decrease, while eGFR slightly increased, and neither reached statistical significance. No serious adverse events were reported, indicating a favorable safety profile for FCM.

Conclusion: The study demonstrated that 100 mg IV FCM is an effective and safe treatment for managing iron deficiency anemia in Indian HD-CKD patients. The significant improvement in Hb, ferritin, and TSAT levels post-FCM administration supports its use as a reliable therapeutic option in this patient population.

Marring effects of chronic kidney disease on the oral cabinet: a case control study

Runal Bansod — 2025-04-28

Background: Patients with kidney diseases are an extremely delicate group of patients. Hence a cooperation between a dentist and a nephrologist is very imperative for a suitable dental treatment of such patients. This would lead to avoidance of severe complications of kidney diseases rendering early diagnosis of the disease. To study the effect of chronic kidney disease on the oral mucosa and inspecting the wide spectrum of oral manifestations in patients with chronic kidney disease.

Methods: The study group consisting of 57 participants including the control group above the age group of 20 years was selected. Patients were selected from a private dialysis center. The study population was divided randomly into three groups, each group consisting of 19 participants. Group I consisted of 19 recently diagnosed chronic renal failure patients who were not on dialysis. Group II consisted of 19 chronic renal failure patients who were on dialysis and Group III consisted of 19 normal subjects as control group.

Results: Various oral manifestations are peculiar of chronic kidney disease and thus the oral cavity should be thoroughly examined in order to inspect these oral findings and treat them accordingly. In the present study oral manifestations such as drug induced melanosis, periodontitis, gingival enlargement, leukoplakia, angular cheilitis, mucosal pallor and oral ulcerations were seen in the study subjects

Conclusions: The oral cavity of chronic kidney disease patients may display a number of oral manifestations which at right time if treated properly may reduce the risk of spread of infections.

Assessing the role of cross-cultural communication in shaping patient perceptions in medical tourism hospitals

Himanshu Tyagi — 2025-04-28

Background: Medical tourism has emerged as a key sector of the global healthcare industry, offering patients access to advanced treatments in foreign countries. While clinical outcomes are crucial, patient satisfaction is profoundly influenced by cross-cultural communication. This study investigates the impact of cultural competence on patient satisfaction in medical tourism, particularly focusing on communication styles and expectations.

Methods: A cross-sectional design was used to survey 1,476 international medical tourists in a government-approved healthcare facility in New Delhi, India. Data collection employed a detailed questionnaire encompassing six main sections, subdivided into 71 items covering verbal and non-verbal communication, cultural beliefs and time orientation. Statistical analyses included exploratory and confirmatory factor analysis, structural equation modelling and multi-group analysis.

Results: The findings revealed a significant positive relationship between patient beliefs in physicians’ cultural competence and patient satisfaction. Intercultural communication expectations partially mediated this relationship. Operational factors such as waiting and consultation times emerged as moderators. The results indicated that providers who adapted communication styles to patients' cultural expectations achieved higher satisfaction rates.

Conclusions: This study highlights the importance of cultural competence in enhancing patient experiences and satisfaction in medical tourism. By addressing diverse cultural expectations and communication styles, healthcare providers can foster trust and improve outcomes. These findings underscore the need for systematic cross-cultural training as a strategic priority in the global medical tourism industry.

Risk factors of acute heart failure after the first episode of acute coronary syndrome

Sai Deepthi Janaki Rani Ivaturi — 2025-04-28

Background: Factors that speed up the development of acute heart failure (AHF) after acute coronary syndrome (ACS), are understudied in developing country like India. Therefore, this study was aimed to determine the risk factor of heart failure (HF) among the post-ACS patients.

Methods: This descriptive cross-sectional study was performed at Government General Hospital (GGH) Srikakulam, Andhra Pradesh, India. 108 patients who were admitted with HF cardiology unit of GGH after ACS from September 2023 to November 2024 were enrolled in the study. An established inclusion and exclusion criteria along with consecutive sampling technique were used for patients’ recruitment. A self-structured proforma was applied to gather data. Data analysis was done in the statistical package for the social sciences (SPSS) version 25.0.

Results: HF was more prevalent among those post-acute coronary syndrome patients who had an age group with 40 years or above (69.23%), male gender (62.82%), anterior wall myocardial infarction (38.46%), reduced ejection fraction (67.90%), left anterior descending artery pathology (17.95%), absence of myocardial revascularization procedure (46.15%), diabetes mellitus (52.56%), hypertension (78.20%), anemia (53.85%), hyperlipidaemia (75.64%), and who had history of smoking (51.28%). A significant number of patients also had chronic kidney disease (23.10%).

Conclusions: Factors such as an age group with 40 years or above, male gender, anterior wall myocardial infarction, reduced ejection fraction, left anterior descending artery pathology, absence of myocardial revascularization procedure, diabetes mellitus, hypertension, anemia, hyperlipidemia and history of smoking, all accelerate the development of HF among post-ACS patients.

Crossword puzzle training and neuroplasticity in mild cognitive impairment (COGIT-2): 78-week, multi-site, randomized controlled trial with cognitive, functional, imaging and biomarker outcomes

Laura A. Wang — 2025-04-11

Background: Cognitive training represents an important potential therapeutic strategy for mild cognitive impairment (MCI). In our recently completed trial, crossword puzzles were superior to computerized cognitive training on Alzheimer's disease assessment scale–cognitive subscale-11 (ADAS-Cog11) and function, correlating with decreased brain atrophy over 78 weeks.

Methods: COGIT-2 is a 78-week, multicenter, clinical trial comparing home-based, high-dose crosswords (4 puzzles per week) to low-dose crosswords (1 puzzle per week) and a health education control group in 240 MCI subjects. Crossword puzzles, administered by the CogniFit research platform, have been designed to have a moderate level of difficulty.

Results: The primary outcome is change in ADAS-Cog14 and the main secondary outcome is change in informant reported daily functioning. Additional outcomes include changes in magnetic resonance imaging (MRI) hippocampal volume and cortical thickness as well as changes in plasma neurofilament light and plasma pTau217.

Conclusions: If the efficacy of computerized crossword puzzle training is confirmed in COGIT-2, crosswords training could become a low-cost, home-based, scalable, cognitive enhancement tool for people at risk for Alzheimer’s disease. The dose comparison will provide useful information on the preferred frequency of crossword puzzle training.

Trial Registration: Trial registration number ClinicalTrials.gov identifier (NCT06601933).

Trace-dosage of lithium for prevention of cognitive declining in mood illnesses: a randomized double-blind, placebo-controlled, study protocol

Paul A. Vöhringer — 2025-04-28

Background: Mood disorders [bipolar disorder (BD) and recurrent unipolar depression] are among the most common mental health conditions worldwide, and are recognized as significant risk factor for development of mild cognitive impairment (MCI) and dementia. Lithium, the gold standard treatment for these mood disorders, has also been suggested as a potential neuroprotective agent, even at trace doses. This study aims to evaluate the effect of trace doses of lithium in preventing cognitive decline in individuals with mood disorders.

Methods: This is randomized, double-blind, placebo-controlled trial involving 250 participants aged 55 to 75 years, all of whom have mood disorders and are not currently receiving lithium therapy. Participants will be randomized into either trace dose lithium (50 mg oral tablets daily) or placebo group, with 125 subjects in each group. All participants will continue their usual clinical treatment and will be followed every six month for five years. The primary outcome measure will be the incidence of MCI or worsening of pre-existing MCI, defined as change from baseline clinical dementia rating scale (CDR) score of 0 to 0.5 (MCI).

Conclusions: If this research demonstrates that trace doses of lithium can prevent the onset or progression of MCI or dementia in patients with mood disorders, it could offer a new therapeutic approach for addressing cognitive decline in this high-risk population, with significant public health implications.

Trial registration: clinicaltrials.gov: NCT06662526.

Innovating CBT-I for cancer survivors: study protocol for a randomized controlled optimization trial

Emma G. Balkind — 2025-04-28

Background: Insomnia is a significant issue in 30-50% of cancer survivors. Our pilot randomized controlled trial of synchronous, virtual cognitive behavioral therapy for insomnia (CBT-I) for cancer survivors suggested that a group format or booster sessions may optimize effects on insomnia and daytime functioning. The goal of this project is to conduct a factorial, randomized controlled trial to optimize synchronous, virtual delivery of CBT-I for cancer survivors.

Methods: We will conduct a 2×2 factorial trial (N=80) to evaluate the optimal combination of two intervention design components: delivery (individual vs. group) and booster sessions (0 vs 3). The primary outcome is change in insomnia severity (insomnia severity index) from T0 (week 0) to T2 (week 8). The secondary outcomes are acute (T0-T1, week 4) and sustained (T0-T3, week 16) changes in insomnia severity, emotional distress, work-related functioning, use of sleep medications, and subjective and objective sleep metrics (measured with sleep diaries and Fitbit). Exploratory aim 1 is to characterize study participation and sleep outcomes among racial and ethnic minority cancer survivors with insomnia. Exploratory aim 2 is to characterize the acceptability of design components using Likert ratings (very low=1 to very high=5, benchmarks=4 or higher) and exit interviews with open-ended responses with probes.

Conclusions: This project will yield multiple deliverables to innovate cancer survivorship care, chiefly an optimized, scalable, virtually delivered intervention that addresses chronic insomnia, one of the most deleterious concerns among the among the steadily increasing number of cancer survivors.

Trial Registration: NCT06181643.

Effect of enhanced external counterpulsation on heart rate variability in ischemic stroke patients: a pre-and post-interventional study protocol

J. M. Janani — 2025-04-28

Background: Stroke is a prominent cause of mortality as well as disability globally. More than 40% of stroke survivors experience complications that last a lifetime. Following an ischemic stroke (IS), abnormalities in the autonomic nervous system (ANS) may influence the probability of another stroke and the healing process. Enhanced external counterpulsation (EECP) is a safe, effective, non-invasive treatment method that enhances blood circulation to the brain and manages ischemic cardiovascular and cerebrovascular diseases. There is a limited amount of literature exploring the effects of EECP on HRV specifically on stroke patients. Hence, the study aims to determine the impact of EECP on HRV in IS patients.

Methods: This single arm pre and post intervention study recruits 35 out of 45 subjects. The intervention will be given 5 days/week/45 minutes a session for 35 sessions. Pre-and post-intervention outcome measures will be measured. After collecting the data, statistical analysis will be done.

Conclusion: The application of EECP may be unlikely to cause any adverse effects in ischemic stroke patients, indicating that EECP may be a safe and effective treatment to improve hand grip strength and QOL in ischemic stroke patients.

Trial registration: Clinical trials (CTRI): CTRI/2023/11/060112.

Caregiver-driven cognitive training program for dementia: a treatment development and feasibility study protocol in Indian population

Aparna Kanmani S. — 2025-04-28

Background: Cognitive training (CT) is an efficacious intervention for promoting experience-dependent neuroplasticity, especially in modifying cognitive decline in neurodegenerative conditions. Despite its immense potential, there exist clinical and logistic challenges in delivering the intervention to the dementia population. Given the cultural context of collectivistic societies like India, where family involvement is integral in illness-related care, a caregiver-supported CT program may overcome current challenges and help promote accessible and affordable dementia care.

Methods: The prospective study holds two main objectives that is to develop a caregiver-driven CT program called the Individualized Cognitive Augmentation Regimen for Elderly (iCARE) and to assess the feasibility of iCARE for mild to moderate dementia. The intervention is designed systematically through literature review, item generation, expert validation, field trials, iterative feedback modification and pilot testing. Rooted in principles of neuroplasticity, iCARE targets the core cognitive abilities of attention, executive functions, language and memory. It employs an integrative approach combining bottom-up and top-down strategies, potentially loading on the frontoparietal or central executive networks. The feasibility testing protocol of iCARE aims to build a sustainable model by empowering caregivers as co-therapists through adequate training, thereby reducing the existing treatment gap for dementia in India.

Conclusion: The interactive and individualized nature of iCARE may contribute to delaying/slowing cognitive decline in dementia patients while supporting caregivers' well-being. This paper addresses the technical 'what,' 'how,' and 'why' questions in developing and feasibility-testing a culturally specific CT program for dementia.

Trial Registration: Clinical Trial Registry of India (7th October 2022) - CTRI/2022/10/046281.

Protocol for a randomized controlled study comparing the efficacy and safety of daily versus alternate day teneligliptin 20 mg in type 2 diabetes mellitus patients

Suave — 2025-04-28

Background: For effective management of type 2 diabetes mellitus (T2DM), in addition to efficacy, safety, compliance and cost play a considerable role. Teneligliptin has long elimination half-life (24 hours) and offers a potential to be administered on alternate days. But there is paucity of robust clinical evidence. This study seeks to compare efficacy and safety of daily and alternate day teneligliptin therapy.

Methods: This is a single-center, open label, parallel group, randomized controlled study. A total of 60 adults suffering from T2DM with HbA1c 7 to 9 %, who received at least 3 months of metformin (≥1000 mg), will be enrolled. The participants will be randomized in 1:1 ratio into two groups (30 participants per group) receiving daily or alternated day teneligliptin 20 mg over and above standard of care for a duration of 3 months. The primary end point is change in HbA1c levels from baseline after 3 months of initiating teneligliptin 20 mg therapy. Data analysis will be done using SYSTAT software (13.2 version for windows, San Jose, CA: Inpixon Inc.) and the Intention-to-Treat approach will be employed for the analysis.

Conclusions: If alternate day teneligliptin add on therapy proves to have comparable efficacy with daily therapy, it will provide us with a safe, efficacious and cost-effective alternative in T2DM patients. This study has potential to bring down the public health and economic burdens associated with management of T2DM.

Trial registration: CTRI number: CTRI/2024/06/068564.