Large Trials Research Articles

Clinical trial evidence supporting FDA approval of novel orphan drugs between 2017 and 2023

Characterization analysis of 87 pivotal clinical trials for 72 novel orphan drugs (76 orphan indications) approved by the FDA from 2017 to 2023 revealed that the clinical trial evidence supporting FDA orphan drug approvals often lacked high-quality designs, which frequently did not incorporate randomization, blinding, placebo or no treatment control, or clinical endpoint-driven methodologies. Additionally, regulatory flexibility was observed in the quantity of clinical trial evidence required, which included choices such as a single trial plus confirmatory evidence, one large multicenter trial or at least two trials. Furthermore, the overall strength of the clinical trial evidence exhibited variations across different orphan drugs and indications, influenced by features such as the therapeutic area and whether the orphan drug was granted accelerated approvals.

Statistical Analysis Plan for the AIRCARD Study: Individual Long-Term Air and Noise Pollution Exposure and Cardiovascular Disease Incidence and Mortality - A Prospective Cohort Study Utilizing DANCAVAS and VIVA Screening Trials.

The AIRCARD study is designed to investigate the relationship between long-term exposure to air and noise pollution and cardiovascular disease incidence and mortality. We aim to conduct a robust prospective cohort analysis assessing the cumulative and differential impacts of air and noise pollution exposure on cardiovascular disease and mortality. This study will adjust for relevant confounders, including traditional cardiovascular risk factors, socioeconomic indicators, and lipid-lowering agents. This prospective cohort study will include 27,022 male participants aged 65-74, recruited from the two large Danish DANCAVAS and VIVA trials, both population-based randomized, multicentered, clinically controlled studies. We will assess long-term exposure to air pollutants using the state-of-the-art DEHM/UBM/AirGIS modeling system and noise pollution through the Nord2000 and SoundPLAN models, covering data from 1979 to 2019. This statistical analysis plan is strictly formulated to predefine the analytical approach for all outcomes and key study variables before data access. The primary analysis will utilize Cox proportional hazards models, adjusted for confounders identified in our cohort (age, body mass index, hypertension, diabetes, smoking status, family history of heart disease, socioeconomic factors, and lipid-lowering agents). This statistical analysis plan further includes Spearman rank correlation to explore inter-pollutant associations. The AIRCARD study addresses global concerns about the impact of air and noise pollution on cardiovascular disease. This research is important for understanding how the pollutants contribute to cardiovascular disease. We aim to provide insights into this area, emphasizing the need for public health measures to mitigate pollution exposure. Our goal is to provide policymakers and healthcare professionals with information on the role of environmental factors in cardiovascular health that could influence global strategies to reduce the cardiovascular disease burden associated with pollution. The design of this SAP ensures transparency and verifiability, considering the complexities of evaluating environmental health impacts over an extended period.

Effect of vitamin D on risk of falls and fractures – The contribution of recent mega-trials

Three recently-completed, large clinical trials in the U.S, New Zealand, and Australia, referred to herein as the ‘mega-trials’, were conducted to determine the impact of supplemental vitamin D on a variety of outcomes including falls and fractures. The trials were similar in design and collectively included over 50,000 generally vitamin D replete, older men and women. The mega-trials established that vitamin D supplementation with the equivalent of 2000 to 3300 IU/d of vitamin D3 had no favorable effect on risk of falls or fractures. This review focuses on specific design elements of the trials and how they likely influenced these trial findings. While these trials were in progress, evidence emerged that circulating 25-hydroxyvitamin D levels have a U-shaped association with risk of falling, raising concern about a potential untoward effect of high dose supplementation. There is compelling evidence that in older, vitamin D- and calcium-insufficient nursing home residents, the combination of vitamin D and calcium in modest replacement doses dramatically reduces the risk of hip and other fractures. Community-dwelling older adults in many populous countries around the globe have widespread vitamin D and calcium insufficiency. It is time to follow the evidence trail and determine the effect of vitamin D and calcium replacement on their risk of falls and fractures.

Gestational weight gain as a mediator of the relationship between pre-pregnancy body mass index and the risk of preterm birth: A four-way decomposition analysis.

The aim of the present study was to examine and quantify whether the association between preterm birth (PTB) and pre-pregnancy body mass index (BMI) is mediated by gestational weight gain (GWG). This is a secondary analysis of a large randomized community non-inferiority trial using a cohort design. The data of 26 101 pregnant women in their first trimester who sought prenatal care and met eligibility criteria were included. The four-way decomposition method was applied to screen for all types of association effects of pre-pregnancy BMI on the risk of PTB. These effects include the total, direct, and various indirect effects including pure mediation via GWG, interactive effects with GWG, and mediated interaction with GWG, all adjusted for potential confounders. Among the study participants, 24 461 (93.7%) had term deliveries, while 1640 (6.3%) experienced PTB. The results of the study showed that there was a positive association between pre-pregnancy BMI among those with BMI more than 25 kg/m2 and the risk of PTB and this association was negatively mediated and interacted by GWG, which differed quantitatively between those who had inadequate, adequate, or excessive GWG. The total association effect showed that the risk was lowest for those who had underweight pre-pregnancy BMI and adequate GWG (excess relative risk [RR]: 0.06, 95% CI: 0.01-0.11, P value: 0.022) and was highest for those who had obese pre-pregnancy BMI and excessive GWG (excess RR: 0.67, 95% CI: 0.35-1.00, P value <0.001). The findings of the present prospective population-based study demonstrated that pre-pregnancy BMI >25 kg/m2 is directly and positively associated with the risk of preterm birth. The highest risk of preterm birth was observed among individuals with an obese pre-pregnancy BMI who also experienced excessive GWG.

Examining nutrition strategies to influence DNA methylation and epigenetic clocks: a systematic review of clinical trials.

Nutrition has powerful impacts on our health and longevity. One of the mechanisms by which nutrition might influence our health is by inducing epigenetic modifications, modulating the molecular mechanisms that regulate aging. Observational studies have provided evidence of a relationship between nutrition and differences in DNA methylation. However, these studies are limited in that they might not provide an accurate control of the interactions between different nutrients, or between nutrition and other lifestyle behaviors. Here we systematically reviewed clinical studies examining the impact of nutrition strategies on DNA methylation. We examined clinical studies in community-dwelling adults testing the effects of nutrition interventions on i) global DNA methylation and its proxies, and ii) epigenetic clocks. We included 21 intervention studies that focused on the effects of healthy nutrition patterns, specific foods or nutrients, as well as the effect of multivitamin or multimineral supplements. In four studies on the methylation effects of healthy dietary patterns, as defined by being rich in vegetables, fruits, whole-grains, and nuts and reduced in the intake of added sugars, saturated fat, and alcohol, two of them suggested that a healthy diet, is associated with lower epigenetic age acceleration, one of them reported increases in global DNA methylation, while another one found no diet effects. Studies examining epigenetic effects of specific foods, nutrients, or mixtures of nutrients were scarce. For both folic acid and polyunsaturated fatty acids, the available independent studies produced conflicting findings. Although more evidence is still needed to draw firm conclusions, results begin to suggest that healthy dietary patterns have positive effects on DNA methylation. Additional evidence from large randomized-controlled clinical trials is needed to support the effects of healthy nutrition on the DNA methylome.

Biomarkers Associated with Depression Improvement in Veterans with Gulf War Illness Using the Low-Glutamate Diet.

Gulf War Illness (GWI) is a chronic multi-symptom neurological disorder affecting veterans of the Gulf War that is commonly comorbid with depression. A secondary data analysis was conducted to examine serum homocysteine and inflammatory cytokines (IFN-γ, IL-6, IL-1β, TNF-α) as potential biomarkers of depression improvement among veterans with GWI after a one-month dietary intervention aimed at reducing excitotoxicity and increasing micronutrients. Analyses, including multiple linear and logistic regression, were conducted in R studio. Dietary adherence was estimated using a specialized excitotoxin food frequency questionnaire (FFQ), and depression was measured using the Center for Epidemiologic Studies Depression (CES-D) scale. After one month on the diet, 52% of participants reported a significant decrease in depression (p < 0.01). Greater dietary adherence (FFQ) was associated with increased likelihood of depression improvement; OR (95% CI) = 1.06 (1.01, 1.11), (p = 0.02). Reduced homocysteine was associated with depression improvement after adjusting for FFQ change (β = 2.58, p = 0.04), and serum folate and vitamin B12 were not mediators of this association. Reduction in IFN-γ was marginally associated with likelihood of depression improvement (OR (95% CI) = 1.11 (0.00, 1.42), (p = 0.06)), after adjustment for potential confounders. Findings suggest that homocysteine, and possibly IFN-γ, may serve as biomarkers for depression improvement in GWI. Larger trials are needed to replicate this work.

Elemental Diet as a Therapeutic Modality: A Comprehensive Review

Elemental diets have been employed for the management of various diseases for over 50 years, with several mechanisms mediating their beneficial effects. Yet, they are underutilized due to poor palatability, access, cost, and lack of awareness regarding their clinical efficacy. Therefore, in this review, we aimed to systematically search and review the literature to summarize the formulation variability, mechanisms of action, clinical applications, and tolerability of the elemental diets in gastrointestinal diseases. While large prospective trials are lacking, elemental diets appear to exhibit objective and subjective clinical benefit in several diseases, including eosinophilic esophagitis, eosinophilic gastroenteritis, inflammatory bowel diseases, small intestinal bacterial overgrowth, intestinal methanogen overgrowth, chemoradiotherapy-associated mucositis, and celiac disease. Although some data support the long-term use of elemental diets as an add-on supplement for chronic pancreatitis and Crohn’s disease, most of the literature on exclusive elemental diets focuses on inducing remission. Therefore, subsequent treatment strategies for maintaining remission need to be adopted in chronic/relapsing diseases. Several mechanistic pathways were identified to mediate the effects of elemental diets, including food additive and allergen-free content, high passive absorption rate, and anti-inflammatory properties. High rates of intolerance up to 40% are seen in the trials where exclusive elemental diets were administered orally due to poor organoleptic acceptability; however, when tolerated, adverse events were rare. Other limitations of elemental diets are cost, access, and lifestyle/social restrictions. Moreover, judicious use is advised in presence of a concomitant restrictive food intake disorders. Elemental diets offer a potentially highly efficacious dietary intervention with minor side effects. Palatability, cost, access, and social restrictions are common barriers of use. Prospective clinical trials are needed to elucidate the role of elemental formulas in the management of individual diseases.

T8 - Association of Baseline Fentanyl Use and Opioid Withdrawal Symptoms During Inpatient Buprenorphine Initiation in a Large Multisite Detoxification Trial

T8 - Association of Baseline Fentanyl Use and Opioid Withdrawal Symptoms During Inpatient Buprenorphine Initiation in a Large Multisite Detoxification Trial

Donor Conditioning and Organ Pre-Treatment Prior to Kidney Transplantation: Reappraisal of the Available Clinical Evidence.

Therapeutic measures aimed at optimising organ function prior to transplantation-whether by conditioning the donor after determination of brain death or by improving organ preservation after kidney removal-have the potential to enhance outcomes after transplantation. The particular advantage is that, unlike any optimised immunosuppressive therapy, a favourable effect can be achieved without side effects for the organ recipient. In recent years, several such measures have been tested in controlled clinical trials on large patient cohorts following kidney transplantation. Hypothermic pulsatile machine perfusion, in particular, has become the focus of interest, but interventions in the donor prior to organ removal, such as the administration of low-dose dopamine until the start of cold perfusion as an example of conditioning antioxidant therapy and therapeutic donor hypothermia in the intensive care unit after brain death confirmation, have also significantly reduced the frequency of dialysis after transplantation with far less effort and cost. With regard to benefits for graft survival, the database for all procedures is less clear and controversial. The aim of this review article is to re-evaluate the available clinical evidence from large multicentre controlled trials, which have also significantly influenced later meta-analyses, and to assess the significance for use in routine clinical practice.

New Horizons of Model Informed Drug Development in Rare Diseases Drug Development.

Model-informed approaches provide a quantitative framework to integrate all available nonclinical and clinical data, thus furnishing a totality of evidence approach to drug development and regulatory evaluation. Maximizing the use of all available data and information about the drug enables a more robust characterization of the risk-benefit profile and reduces uncertainty in both technical and regulatory success. This offers the potential to transform rare diseases drug development, where conducting large well-controlled clinical trials is impractical and/or unethical due to a small patient population, a significant portion of which could be children. Additionally, the totality of evidence generated by model-informed approaches can provide confirmatory evidence for regulatory approval without the need for additional clinical data. In the article, applications of novel quantitative approaches such as quantitative systems pharmacology, disease progression modeling, artificial intelligence, machine learning, modeling of real-world data using model-based meta-analysis and strategies such as external control and patient-reported outcomes as well as clinical trial simulations to optimize trials and sample collection are discussed. Specific case studies of these modeling approaches in rare diseases are provided to showcase applications in drug development and regulatory review. Finally, perspectives are shared on the future state of these modeling approaches in rare diseases drug development along with challenges and opportunities for incorporating such tools in the rational development of drug products.

Training and Verification Requirements for Interpretation of Cardiac CT and MRI: AJR Expert Panel Narrative Review.

The use of cardiac CT and MRI is rapidly expanding based on strong evidence from large international trials. The number of physicians competent to interpret cardiac CT and MRI may be unable to keep pace with the increasing demand. Societies and organizations have prescribed training requirements for interpreting cardiac CT and MRI, with recent updates focusing on the increased breadth of competency that is now required due to ongoing imaging advances. In this AJR Expert Panel Narrative Review, we discuss several aspects of cardiac CT and MRI training, focusing on topics that are uncertain or not addressed in existing society statements and guidelines, including determination of competency in different practice types in real-world settings and the impact of artificial intelligence on training and education. The article is intended to guide updates in professional society training requirements and also inform institutional verification processes.

Targeted biopsy of the prostate.

Diagnostic multiparametric MRI of the prostate has steadily evolved over the last three decades and can now reliably depict the dominant tumor in most men with prostate cancer. In response, several methods of targeted biopsy to direct tissue sampling of suspected tumor foci seen at multiparametric MRI have been developed and successfully tested in recent years, including software-assisted MRI-ultrasound (US) fusion biopsy and direct MRI-guided in-bore biopsy. These advances are leading to a sea change in the approach to prostate cancer diagnosis, with the traditional approach of blind systematic biopsy increasingly being replaced by MRI directed targeted biopsy. This review aims to describe the current status of targeted biopsy, with an emphasis on the relative accuracy of different techniques. The results of several critical large multicenter trials are presented, while unanswered questions that require more research are highlighted.

Imatinib Mesylate Causes Potential Cardiac Dysfunction in Patients With Chronic Myeloid Leukemia: the Results of a Case-control Study.

Unlike second-generation tyrosine kinase inhibitors, effects of imatinib on the cardiovascular (CV) system are debatable. The current case-control study aimed to evaluate the CV effects of imatinib in patients with chronic myeloid leukemia (CML) using non-invasive 2D-echocardiography testing. Patients with CML ≥ 13 years attending the adult haematology clinic of a tertiary care hospital in north India were prospectively enrolled over 1.5 years. The study population (n = 110) consisted of 35 newly diagnosed patients (treatment-naïve group) and 75 patients under imatinib therapy ≥ 1 year (treated group). All the eligible patients were subjected to 2D-echocardiography to calculate pulmonary artery systolic pressure (PASP), left ventricular ejection fraction (LVEF) and deceleration time (DT). These parameters were compared between the two groups. P-value < 0.05 was considered statistically significant. The median age of study population was 40 years (range, 13-73) and M:F ratio was 1.14:1. Both the groups had similar demographics at the diagnosis including CV risk factors. The median PASP of the treated group was 2 mm Hg higher than the treatment-naïve group (25 vs 23 mm Hg, p-value = 0.919). The median LVEF of the treated group was 3.2% lower than the treatment-naïve group (58.5% vs 61.72%, p-value = 0.577). The median DT of the treated group was 7 ms shorter than treatment-naïve group (211 vs 204 ms, p-value = 0.411). Imatinib causes potential cardiac dysfunction in patients with CML. Large scale prospective follow-up trials in the same cohort of patients are needed to validate the findings of our study.

Aticaprant, a kappa opioid receptor antagonist, and the recovered 'interest and pleasure' in the concept of major depressive disorder.

Lack of positive mood and anhedonia probably are the most specific depressive symptoms. Anhedonia is a multifaceted concept: the clinical language describes anticipatory/consummatory anhedonia and sensory/social anhedonia while the cognitive neuroscience language describes readiness for reward, energy expenditure to attain reward, updating reward presence and value. Mounting evidence supports the potential of kappa-opioid receptor (KOR) antagonists as novel pharmacotherapies for major depressive disorder : aticaprant is a potent, selective, short-acting KOR antagonist. The fast-fail approach evaluated the impact of aticaprant on the brain circuitry hypothesized to mediate anhedonia and significantly increased fMRI activation in the ventral striatal activation during reward anticipation as compared to placebo; the aticaprant induced changes in the self-reported psychological measures of anhedonia were rather inconsistent. The recently reported results of a phase 2a randomized, double-blind, placebo-controlled trial investigating the efficacy and safety of aticaprant, co-administered to an oral SSRI/SNRI antidepressant in depressed patients who had an inadequate response to 1 or 2 antidepressants. The improvement from baseline favoured the co-administration of aticaprant over the co-administration of placebo at all time points (during 6 weeks), and this was confirmed by higher response rates with aticaprant. A mid-split of patients with higher or lower than median anhedonia also showed that the patients with higher baseline anhedonia had the largest decrease on the MADRS. Tolerability and safety were reassuring. These promising results of the co-administration of aticaprant to an SSRI/SNRI in depressed patients with prominent anhedonia support he further investigation of aticaprant in larger trials.

A randomised trial of malaria vaccine R21/Matrix-M™ with and without antimalarial drugs in Thai adults

In preparation for mass vaccinations with R21/Matrix-M™ combined with mass administrations of dihydroartemisinin, piperaquine, and a single low dose primaquine we assessed the tolerability, safety, and potential interactions of this combination affecting immunogenicity or pharmacokinetics. 120 healthy Thai volunteers were randomised to receive either antimalarials combined with vaccinations (n = 50), vaccinations alone (n = 50), or antimalarials only (n = 20). Three rounds of vaccines and antimalarials were administered one month apart. The vaccine was well tolerated alone and in combination with the antimalarials. None of the participants failed completion of the 3-dose vaccine course. There was no significant difference in the vaccine immunogenicity or in the pharmacokinetics of piperaquine given individually or in combination. This study supports proceeding to a large trial of mass vaccinations with R21/Matrix-M™ combined with mass antimalarial administration in Bangladesh.

Lost in the plot: missing visual elements in Kaplan-Meier plots of phase III oncology trials.

Missing visual elements (MVE) in Kaplan-Meier (KM) curves can misrepresent data, preclude curve reconstruction, and hamper transparency. This study evaluated KM plots of phase III oncology trials. MVE were defined as an incomplete y-axis range or missing number at risk table in a KM curve. Surrogate endpoint KM curves were additionally evaluated for complete interpretability, defined by (1) reporting the number of censored patients and (2) correspondence of the disease assessment interval with the number at risk interval. Among 641 trials enrolling 518 235 patients, 116 trials (18%) had MVE in KM curves. Industry sponsorship, larger trials, and more recently published trials were correlated with lower odds of MVE. Only 3% of trials (15 of 574) published surrogate endpoint KM plots with complete interpretability. Improvements in the quality of KM curves of phase III oncology trials, particularly for surrogate endpoints, are needed for greater interpretability, reproducibility, and transparency in oncology research.

New pacing strategies for heart failure

In patients with areduced left ventricular (LV) systolic function (ejection fraction < 35%) and aleft bundle branch block with a QRS duration > 130 ms, cardiac resynchronization therapy (CRT) can contribute to an improvement in the quality of life and areduction in mortality. The resynchronization is mostly achieved by pacing via an epicardial LV lead in the coronary sinus; however, this approach is often limited by the patient's venous anatomy and an increase in the stimulation threshold over time. In addition, up to 30% of patients do not respond to the intervention. New treatment approaches involve direct stimulation of the conduction system by pacing of the bundle of His or left bundle branch. This enables a more physiological propagation of the stimulus. Pacing of the left bundle branch is achieved by advancing the lead into the right ventricle and screwing it deep into the interventricular septum. Due to the relatively large target area of the left bundle branch the success rate is very high (currently > 90%). Observational studies have shown agreater reduction in the QRS duration, amore pronounced improvement in systolic function and alower hospitalization rate for heart failure associated with conduction system pacing compared to CRT using acoronary sinus lead. These findings have been confirmed in small randomized trials. Therefore, the use of left bundle branch pacing should be considered not only as abail out in the case of failed resynchronization using coronary sinus lead placement but increasingly also as an initial pacing strategy. The results of the first large randomized trials are expected to be released in late 2024.

The Landscape of Care for Women Veterans with Cancer: An Evidence Map.

Women are the fastest growing veteran group in the US and the number of women veterans (WVs) with cancer is rising; however, little is known about this population. Cancer care for WVs is complex and it is essential to understand their unique needs and care coordination challenges to provide evidence-based care. The purpose of this review is to map the quantity, distribution, and characteristics of literature describing cancer and its treatment among WVs. We searched MEDLINE (via PubMed), Embase (Elsevier), and Web of Science Core Collection (Clarivate) from inception through January, 2024. Publications were eligible that reported gender-specific data on any aspect of cancer care among WVs. Data was abstracted by a single investigator with over-reading. Forty-six reports were included; 44 were observational and 19 had a women-only sample. There were no interventional reports and no qualitative reports had a patient sample. Breast cancer was the most commonly addressed (n = 19). There were six additional reports on sex-specific cancers. Many reports used large VA databases or previous trial data, creating the potential for patient overlap between reports. Among VA-specific areas of interest, only three reports evaluated the potential implications of racial differences and only two included a transgender population. No reports examined the effects of toxic exposures on cancer. Within the NCI Cancer Control Continuum, crosscutting areas were more commonly represented; over half (25) of the reports addressed epidemiology. There were few reports on focus areas and little overlap between focus and crosscutting areas. Existing literature provides an inadequate understanding of the population of WVs with cancer. There is scant information regarding the population of WVs with cancer, their care preferences or experiences, or how to best identify and address unmet healthcare needs. It is imperative to expand research to provide evidence-based care for this population.

Left Atrial Strain as a Predictor of Early Anthracycline-Induced Chemotherapy-Related Cardiac Dysfunction: A Pilot Systematic Review and Meta-Analysis.

Background: Chemotherapy-related cardiac dysfunction (CTRCD) significantly affects patients undergoing anthracycline (AC) therapy, with a prevalence ranging from 2% to 20%. Reduced left ventricular ejection fraction (LVEF) and left ventricular global longitudinal strain (LV GLS) are prognostic parameters for CTRCD detection. Our study aimed to investigate the role of emerging parameters such as left atrial strain (LAS). Methods: We searched multiple databases for studies comparing LAS changes post-AC versus pre-AC therapy in patients with cancer. Primary outcomes included left atrial reservoir strain (LASr), left atrial conduit strain (LAScd), and left atrial contractile strain (LASct). RevMan (v5.4) was used to pool the standardized mean difference (SMD) under a random effects model, with p < 0.05 as the threshold for statistical significance. Results: In an analysis of 297 patients across five studies, AC therapy significantly lowered LASr (SMD = -0.34, 95% CI:-0.55, -0.14, I2 = 0%, p = 0.0009) and LAScd (SMD = -0.41, 95% CI: -0.59, -0.23, I2 = 0%, p < 0.00001) levels. Conversely, LASct demonstrated no significant change (SMD = 0.01, 95% CI: -0.21, 0.23, I2 = 9%, p = 0.95). AC therapy also significantly reduced LV GLS (SMD = -0.31, 95% CI: -0.51, -0.11, I2 = 0%, p = 0.003). While not statistically significant, LVEF decreased (SMD = -0.20, 95% CI: -0.42, 0.03, I2 = 0%, p = 0.09), and left atrial volume index trended higher (SMD = 0.07, 95% CI: -0.14, 0.27, I2 = 0%, p = 0.52) after AC therapy. Conclusions: AC treatment led to reduced LAS and LV GLS values, indicating its potential as an early CTRCD indicator. Larger trials are required to fully explore their clinical significance.

How Intravesical Platelet-Rich Plasma Can Help Patients with Interstitial Cystitis/Bladder Pain Syndrome: A Comprehensive Scoping Review.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a condition characterized by chronic inflammation that affects the bladder. The study was aimed at evaluating the effectiveness of intravesical platelet-rich plasma (PRP) injections in patients with IC/BPS. We conducted a comprehensive search strategy to involve studies that investigate the efficacy of intravesical PRP injections or instillations over different time intervals. Various outcome measures were assessed, including pain scores, functional outcomes, urodynamic parameters, and surface expressions on the urothelium. Our search strategy revealed 1,125 studies. After screening, ten articles met the inclusion criteria. Intravesical PRP significantly reduced the visual analog scale (VAS) compared with baseline scores. Several clinical trials reported significant improvements in the global response rate (GRA), O'Leary-Sant Symptom (OSS) questionnaire, Interstitial Cystitis Symptom Index (ICSI), and Interstitial Cystitis Problem Index (ICPI). Urodynamic parameters such as maximum flow rate (Qmax) and post-voiding residual (PVR) showed significant improvements in some studies. The study concluded that intravesical PRP injections could be a promising effective treatment option for IC/BPS patients by their significant ability to reduce pain. However, improvement of urodynamic and functional outcomes is still not clear. Further large comparative trials are still warranted to assess the efficacy of PRP instillation.