Rate of Serious Adverse Events Associated with Diazoxide Treatment of Patients with Hyperinsulinism

2019 ◽  
Vol 91 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Paul Thornton ◽  
Lisa Truong ◽  
Courtney Reynolds ◽  
Tyler Hamby ◽  
Jonathan Nedrelow
Keyword(s):  
Pulmonary Hypertension ◽  
Adverse Events ◽  
Retrospective Analysis ◽  
First Line ◽  
Serious Adverse Events ◽  
Infants Of Diabetic Mothers ◽  
Drug Agency ◽  
Different Types ◽  
The Difference ◽  
Diabetic Mothers

Introduction: Diazoxide is the first line and only Federal Drug Agency approved pharmacological agent for the treatment of hyperinsulinism. Its use has increased over the years to include patients with various genetic forms of hyperinsulinism, perinatal stress hyperinsulinism and infants of diabetic mothers with more babies than ever being exposed to this therapy. Methods: We performed a retrospective analysis of 194 patients with hyperinsulinism in our clinic and looked for those who had experienced serious adverse events (SAE) including pulmonary hypertension and neutropenia. We compared the rates of SAE in the different types of hyperinsulinism. Results: Out of 194 patients with hyperinsulinism, 165 (85.1%) were treated with diazoxide. There were 17 SAEs in 16 patients including 8 cases of pulmonary hypertension and 8 of neutropenia. These data show that overall the frequency of SAE associated with diazoxide use is 9.7%, but that those with perinatal stress hyperinsulinism have a much higher rate than those with genetic forms of hyperinsulinism (16.7 vs. 3.6%; p = 0.01). We also found diazoxide is associated with pulmonary hypertension (4.8% of patients treated). Although more patients with perinatal stress hyperinsulinism (7.6%) were affected than genetic hyperinsulinism (1.2%), the difference was not significant (p = 0.088). Conclusion: The rate of SAEs associated with (not necessarily caused by) diazoxide has been demonstrated. The rate of SAE in newborns with perinatal stress hyperinsulinism is significantly higher than that of otherwise healthy babies with genetic forms of hyperinsulinism, suggesting that caution should be used when prescribing diazoxide to this population. This information should help balance the risk benefit of treatment and provide guidance on screening for these complications in the population of treated patients.

scholarly journals Randomized, Phase III Trial of First-Line Figitumumab in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone in Patients With Advanced Non–Small-Cell Lung Cancer

2014 ◽  
Vol 32 (19) ◽  
pp. 2059-2066 ◽  
Author(s):  
Corey J. Langer ◽  
Silvia Novello ◽  
Keunchil Park ◽  
Maciej Krzakowski ◽  
Daniel D. Karp ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
First Line ◽  
Serious Adverse Events

Purpose Figitumumab (CP-751,871), a fully human immunoglobulin G2 monoclonal antibody, inhibits the insulin-like growth factor 1 receptor (IGF-1R). Our multicenter, randomized, phase III study compared figitumumab plus chemotherapy with chemotherapy alone as first-line treatment in patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Patients with stage IIIB/IV or recurrent NSCLC disease with nonadenocarcinoma histology received open-label figitumumab (20 mg/kg) plus paclitaxel (200 mg/m2) and carboplatin (area under the concentration-time curve, 6 mg · min/mL) or paclitaxel and carboplatin alone once every 3 weeks for up to six cycles. The primary end point was overall survival (OS). Results Of 681 randomly assigned patients, 671 received treatment. The study was closed early by an independent Data Safety Monitoring Committee because of futility and an increased incidence of serious adverse events (SAEs) and treatment-related deaths with figitumumab. Median OS was 8.6 months for figitumumab plus chemotherapy and 9.8 months for chemotherapy alone (hazard ratio [HR], 1.18; 95% CI, 0.99 to 1.40; P = .06); median progression-free survival was 4.7 months (95% CI, 4.2 to 5.4) and 4.6 months (95% CI, 4.2 to 5.4), respectively (HR, 1.10; P = .27); the objective response rates were 33% and 35%, respectively. The respective rates of all-causality SAEs were 66% and 51%; P < .01). Treatment-related grade 5 adverse events were also more common with figitumumab (5% v 1%; P < .01). Conclusion Adding figitumumab to standard chemotherapy failed to increase OS in patients with advanced nonadenocarcinoma NSCLC. Further clinical development of figitumumab is not being pursued.

Imatinib Long Term Effects (ILTE) Study: An Independent, International Study in CML Patients.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1099-1099
Author(s):  
Carlo Gambacorti-Passerini ◽  
Dong-Wook Kim ◽  
François-Xavier Mahon ◽  
Giuseppe Saglio ◽  
Fabrizio Pane ◽  
...  
Keyword(s):  
Adverse Events ◽  
International Study ◽  
Imatinib Treatment ◽  
Long Term Effects ◽  
First Line ◽  
Eligibility Criteria ◽  
Serious Adverse Events ◽  
Second Cancers

Abstract Imatinib is an effective first line therapy for chronic myeloid leukemia (CML) and has substantially changed its biological and clinical behavior. Durable complete cytogenetic responses (CCyR) were reported in the majority of patients, with a rather benign side effect profile, despite the ‘off target’ inhibition of several other kinases, including Kit, PDGFR and Lck. Since available information is largely based on industry-sponsored trials and long-term field studies are lacking, the ILTE study was conceived as an industryindependent, academic, multicenter trial supported by the Italian Drug Safety Agency (AIFA). ILTE is an international study on a retrospective cohort and includes 31 centers in Europe, North/South America, Africa and Asia; therefore it is uniquely positioned to present a global picture of imatinib long-term effects. Consecutive patients with Ph+ CML who started imatinib between 01 September 1999 and 31 December 2004 were eligible if they were in Complete Cytogenetic Response (CCyR) after two years of imatinib treatment. Study endpoints were survival, serious adverse events (SAE, including second cancers), toxicities not qualifying as SAE (NSAE) but judged by the referring physician as substantially impacting quality of life, loss of CCyR, and development of PCR negativity. A total of 957 patients were enrolled, 92% of which met eligibility criteria. The median age of eligible patients was 50 (range 15–92) years; 59% of patients were males and the median follow-up was 3.1 years (excluding the first 2 years of treatment). As of Dec. 31 2007, 2564 person years were available for analysis. Eleven deaths were observed (only 3 of them caused by relapsed CML), with a standardized rate of 0.4/100 person years and an observed/expected ratio of 0.48 (95% CI = 0.24–0.85). One-hundred SAE were recorded (rate 3.9/100 person years, most frequent type “heart failure”), with 21% being considered related to imatinib. Second cancers were documented in 28 patients (rate 1.1/100 person years), with an observed/expected ratio of 1.27 (95% CI = 0.84–1.84). Among the 576 NSAE recorded (0.65/patient) the most frequent types were “edema, cramps, skin fragility, diarrhea”; 71% of them were related to imatinib. A total of 12 patients (1.4 %) discontinued imatinib because of toxicities during the period of observation. Thirty-four patients lost CCyR, corresponding to a rate of 1.4/100 person years (1.0 in patients with imatinib as first-line treatment, 1.5 in patients who were treated with imatinib &gt;6 months after diagnosis), with stable or increasing rates over time. Finally, 214 patients (24.5%) developed durable (&gt; 1 year) PCR negativity. In conclusion, the first report from ILTE shows that CML patients on imatinib die unfrequently of CML related causes, do not appear to have substantially higher second cancer rates than the general population, have mortality rates lower than expected in an age/sex matched population and do not show new types of imatinib-related adverse events. They also experience a low but steady rate of loss of CCyR and develop PCR negativity in approximately ¼ of cases. Follow-up and further analysis are ongoing. (Presented on behalf of the ILTE Investigators group)

Imatinib Long Term Effects (ILTE) Study: An International Study to Evaluate Long-Term Effects in CML Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2199-2199
Author(s):  
Dong-Wook Kim ◽  
Laura Antolini ◽  
François-Xavier Mahon ◽  
Francois Guilhot ◽  
Michael Deininger ◽  
...  
Keyword(s):  
Adverse Events ◽  
Conflicts Of Interest ◽  
International Study ◽  
Imatinib Treatment ◽  
Long Term Effects ◽  
First Line ◽  
Serious Adverse Events ◽  
Second Cancers

Abstract Abstract 2199 Poster Board II-176 Imatinib is an effective first line therapy for chronic myeloid leukemia (CML) and has substantially changed its biological and clinical behavior. Durable complete cytogenetic responses (CCyR) were reported in the majority of patients, with a rather benign side effect profile, despite the ‘off target’ inhibition of several other kinases, including Kit, PDGFR and Lck. Since available information is largely based on sponsored trials and long-term field studies are lacking, the ILTE study was conceived as an independent, academic, multicenter trial supported by the Italian Drug Safety Agency (AIFA) and Regione Lombardia. ILTE is an international study on a retrospective cohort and includes 31 centers in Europe, North/South America, Africa, Middle East and Asia; therefore it is uniquely positioned to present a global picture of imatinib long-term effects. Consecutive patients with Ph+ CML who started imatinib between 01 September 1999 and 31 December 2004 were eligible if they were in CCyR after two years of imatinib treatment. Study endpoints were (a) survival, (b), serious adverse events (SAE, including second cancers), (c) toxicities not qualifying as SAE (NSAE) but judged by the referring physician as substantially impacting quality of life, (d) loss of CCyR, and (e) development of PCR negativity. A total of 948 patients were enrolled, 88% of which met eligibility criteria after centers were visited and monitored. The median age of eligible patients was 51 (range 18-92) years; 59% of patients were males and the median follow-up was 4.0 years (excluding the first 2 years of treatment). As of Dec. 31 2008, 3255 person years were available for analysis. Twenty one deaths were observed (only 6 of them [28%] caused by relapsed CML), with a standardized rate of 0.6/100 person years and an observed/expected ratio of 0.7 (95% CI = 0.43-1.07, p=ns). A total of 138 SAE were recorded (rate 4.2/100 person years, most frequent type “heart failure”), with 19.5% being considered related to imatinib. Second cancers were documented in 29 patients (rate 0.9/100 person years), with an observed/expected ratio of 1.02. Among the 761 NSAE recorded (rate 23.4/100 person years) the most frequent types were cramps, asthenia,edema, skin fragility, diarrhea; 69% of them were considered related to imatinib. A total of 18 patients (2.2 %) discontinued imatinib because of toxicities during the period of observation. Forty patients lost CCyR, corresponding to a rate of 1.3/100 person years (1.0 in patients with imatinib as first-line treatment, 1.4 in patients who were treated with imatinib >6 months after diagnosis), with stable or increasing rates over time. Finally, 256 patients (36.0 %) developed durable (> 1 year) PCR negativity. In conclusion, this report from ILTE shows that CML patients on imatinib die unfrequently of CML related causes, do not appear to have substantially higher second cancer rates than the general population, have mortality rates similar to an age/sex matched population and do not show new types of imatinib-related adverse events. They also experience a low but steady rate of loss of CCyR and develop PCR negativity in approximately 1/3 of cases. Follow-up and further analysis are ongoing. (Presented on behalf ofthe ILTE Investigators group) Disclosures: No relevant conflicts of interest to declare.

Capecitabine Versus Classical Cyclophosphamide, Methotrexate, and Fluorouracil As First-Line Chemotherapy for Advanced Breast Cancer

2011 ◽  
Vol 29 (34) ◽  
pp. 4498-4504 ◽  
Author(s):  
Martin R. Stockler ◽  
Vernon J. Harvey ◽  
Prudence A. Francis ◽  
Michael J. Byrne ◽  
Stephen P. Ackland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Advanced Breast Cancer ◽  
Tumor Response ◽  
Progression Free Survival ◽  
Advanced Breast ◽  
First Line ◽  
Serious Adverse Events ◽  
Objective Tumor Response ◽  
Line Chemotherapy

Purpose We compared oral capecitabine, administered intermittently or continuously, versus classical cyclophosphamide, methotrexate, and fluorouracil (CMF) as first-line chemotherapy for women with advanced breast cancer unsuited to more intensive regimens. Patients and Methods Three hundred twenty-three eligible women were randomly assigned to capecitabine administered intermittently (1,000 mg/m2 twice daily for 14 of every 21 days; n = 107) or continuously (650 mg/m2 twice daily for 21 of every 21 days; n = 107), or to classical CMF (oral cyclophosphamide 100 mg/m2 days 1 to 14 with intravenous methotrexate 40 mg/m2 and fluorouracil 600 mg/m2 on days 1 and 8 every 28 days; n = 109). The primary end point was quality-adjusted progression-free survival (PFS); secondary end points included PFS, overall survival (OS), objective tumor response, and adverse events. Intermittent and continuous capecitabine were to be compared first and, if similar (P > .05), combined for definitive comparisons versus CMF. Results Quality-adjusted PFS (P = .2), objective tumor response rate (20%; P = .8), and PFS (median, 6 months; hazard ratio [HR], 0.86; 95% CI, 0.67 to 1.10; P = .2) were similar in women assigned capecitabine versus CMF. OS was longer in women assigned capecitabine rather than CMF (median, 22 v 18 months; HR, 0.72; 95% CI, 0.55 to 0.94; P = .02). Febrile neutropenia, infection, stomatitis, and serious adverse events were more common with CMF; hand-foot syndrome was more common with capecitabine. Conclusion Capecitabine improved OS by being similarly active, less toxic, and more tolerable than CMF. Capecitabine is a good first-line chemotherapy option for women with advanced breast cancer who are unsuited to more intensive regimens.

Pharmacokinetics of Tecarfarin and Warfarin in Patients with Severe Chronic Kidney Disease

2017 ◽  
Vol 117 (11) ◽  
pp. 2026-2033 ◽  
Author(s):  
Detlef Albrecht ◽  
Mintu Turakhia ◽  
Daniel Ries ◽  
Thomas Marbury ◽  
William Smith ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Adverse Events ◽  
Plasma Concentrations ◽  
Anticoagulation Therapy ◽  
Serious Adverse Events ◽  
Single Dose Study ◽  
Cyp2c9 Genotype ◽  
The Difference ◽  
Repeated Dosing

AbstractChronic kidney disease (CKD) complicates warfarin anticoagulation partially through its effect on CYP2C9 activity. Tecarfarin, a novel vitamin K antagonist, is not metabolized by CYP2C9. To evaluate the effect of CKD on their metabolism, we measured PK parameters of warfarin and tecarfarin in subjects with and without CKD. CKD subjects with estimated glomerular filtration rate < 30 mL/min not on dialysis (n = 13) were matched to healthy volunteers (HVs) (n = 10). Each subject was randomized to either warfarin 10 mg or tecarfarin 30 mg and was later crossed over to the other drug. PK parameters were measured following each drug. Mean plasma concentrations of (S)-warfarin and (R,S)-warfarin were higher (44 and 27%, respectively) in the subjects with CKD than in the healthy subjects. Both of these values fell outside of the 90% confidence interval of equivalence. For tecarfarin, the difference was less than 15% higher. Elimination half-life (t 1/2) increased by 20% for (S)-warfarin and by 8% for (R,S)-warfarin and decreased by 8% for tecarfarin. The mean plasma concentration for tecarfarin's inactive metabolite ATI-5900 increased by approximately eightfold. CKD increased the effect of CYP2C9 genetic variation on (S)-warfarin and (R,S)-warfarin metabolism. Tecarfarin exposure was similar between the HVs and the CKD subjects regardless of CYP2C9 genotype. There were neither serious adverse events (SAEs) nor treatment-emergent adverse events (TEAEs) for any subject in the study. CKD inhibits metabolism of (S)-warfarin and (R,S)-warfarin, but not tecarfarin. The safety of repeated dosing of tecarfarin in CKD patients remains unknown. However, if the PK findings of this single-dose study are present with repeated dosing, tecarfarin may lead to dosing that is more predictable than warfarin in CKD patients who require anticoagulation therapy.

scholarly journals The safety and efficacy of mesenchymal stem cells in the treatment of COVID-19-associated pneumonia: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Junwu Wang ◽  
Pengzhi Shi ◽  
Dong Chen ◽  
Shuguang Wang ◽  
Pingchuan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adverse Events ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Control Group ◽  
Serious Adverse Events ◽  
Safe Method ◽  
Radiographic Outcomes ◽  
The Difference

Mesenchymal stem cells (MSCs) therapy is considered one of the most promising treatments in the context of the coronavirus disease 2019 (COVID-19) pandemic. However, the safety and effectiveness of MSCs in the treatment of COVID-19-associated pneumonia patients need to be systematically reviewed and analyzed. Two independent researchers searched for the relevant studies published between October 2019 and April 2021 in PubMed, Embase, Cochrane Library, WAN FANG, and CNKI databases. A total of 22 studies involving 371 patients were included in the present study. MSCs were administered in 247 participants, and MSCs were allogeneic from umbilical cord, adipose tissue, menstrual blood, placenta, Wharton's jelly, or unreported sources. Combined results found that MSCs group significantly reduced the incidence of adverse events (OR = 0.43, 95%CI. = 0.22~0.84, P = 0.01) and mortality (OR = 0.17, 95%CI. = 0.06~0.49, P < 0.01), and the difference compared with control group was statistically significant. No MSCs treat-related serious adverse events were reported. The lung function and radiographic outcomes, and biomarker levels of inflammation and immunity all showed improvement trends. Therefore, MSCs therapy is an effective and safe method in the treatment of COVID-19-associated pneumonia and shows advantages in less adverse events and mortality. However, a standard and effective MSCs treatment program needs to be developed.

Pembrolizumab plus chemotherapy for previously untreated, HER2-negative unresectable or metastatic advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: KEYNOTE-859.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS263-TPS263
Author(s):  
Josep Tabernero ◽  
Yung-Jue Bang ◽  
Eric Van Cutsem ◽  
Charles S. Fuchs ◽  
Yelena Y. Janjigian ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Treatment Withdrawal ◽  
First Line ◽  
Serious Adverse Events ◽  
End Points ◽  
Expression Status

TPS263 Background: For patients with unresectable, locally advanced recurrent or metastatic G/GEJ cancer, the standard of care includes a fluoropyrimidine plus a platinum-based agent as first-line therapy. The PD-1 inhibitor pembrolizumab has demonstrated durable antitumor activity in this patient population across lines of therapy. Herein, we describe the randomized, double-blind, phase 3 KEYNOTE-859 trial (NCT03675737) of first-line pembrolizumab plus chemotherapy in patients with advanced G/GEJ adenocarcinoma. Methods: Patients with histologically or cytologically confirmed, locally advanced unresectable or metastatic G/GEJ adenocarcinoma with known PD-L1 expression status, HER2-negative disease, measurable disease per RECIST v1.1, and ECOG performance status of 0 or 1 will be randomly assigned 1:1 to receive pembrolizumab plus chemotherapy or placebo plus chemotherapy. Randomization will be stratified by geographic region (Europe/Israel/North America/Australia vs Asia vs rest of world), PD-L1 tumor expression status (combined positive score < 1 vs ≥1), and combination chemotherapy (FP vs CAPOX). Pembrolizumab or placebo will be administered at 200 mg IV every 3 weeks (Q3W). The chemotherapy regimen will be investigator’s choice of FP (continuous infusion of 5-fluorouracil [800 mg/m2/day on days 1-5 of each cycle] plus IV cisplatin [80 mg/m2] Q3W) or CAPOX (oral capecitabine [1000 mg/m2 twice daily on days 1-14 of each cycle] plus IV oxaliplatin [130 mg/m2 on day 1 of each cycle] Q3W). Duration of cisplatin or oxaliplatin may be capped at 6 cycles per local country guidelines; treatment with 5-fluorouracil or capecitabine may continue per protocol. Treatment with pembrolizumab or placebo will continue for ≤35 administrations (~2 years) or until disease progression, unacceptable toxicity, intercurrent illness that prevents further administration of treatment, investigator decision, or noncompliance. Imaging will be performed at screening and subsequently every 6 weeks until disease progression, start of new anticancer treatment, withdrawal of consent, or death. Adverse events will be monitored throughout the study from the time of randomization to 30 days after the last dose of study treatment (90 days for serious adverse events). The dual primary end points are OS and PFS per RECIST v1.1 as assessed by blinded independent central review (BICR). Secondary end points include ORR and DOR per RECIST v1.1 as assessed by BICR, safety, and tolerability. Enrollment is ongoing. Clinical trial information: NCT03675737.

Retrospective cohort study on the risk factors of admission due to serious adverse events during S-1 (tegaful, gimeracil, oteracil potassium) containing chemotherapy for gastric cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 141-141
Author(s):  
Yasuyuki Kawamoto ◽  
Satoshi Yuki ◽  
Yoshimitsu Kobayashi ◽  
Koji Oba ◽  
Hideyuki Hayashi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Gastric Cancer ◽  
Adverse Events ◽  
Odds Ratio ◽  
Univariate Analysis ◽  
Multivariate Logistic Regression Model ◽  
First Line ◽  
Serious Adverse Events ◽  
Exact Test ◽  
Line Chemotherapy

141 Background: S-1 (tegaful, gimeracil, oteracil potassium) containing regimens are widely used as first line chemotherapy for metastatic or unresectable gastric cancer in Japan. Because patients often need admission due to serious adverse events (SAE) during chemotherapy, it is important to predict admission. We retrospectively investigated the risk factors of admission due to SAE during first line chemotherapy which contained S-1. Methods: We retrospectively analyzed the patients who began to receive S-1 containing chemotherapy for the first line chemotherapy at our institution from January 2005 to December 2010 by medical records. Association between baseline characteristics and admission due to SAE were evaluated by Fisher’s exact test, t-test or Mann-Whitney test. Age, sex, S-1 dose (mg/m2) and other factors which significantly associated in the univariate analysis were evaluated in the multivariate logistic regression model. Results: One hundred nine patients were assessed. Admission due to SAE were observed in 24 patients (34 times), and tended to occur before 2nd cycle had ended. Multivariate analysis suggested that hypoalbuminemia was a risk factor of admission due to all SAE (Odds ratio 0.15, 95% C.I. 0.05 - 0.44, P = 0.0005). It is suggested that S-1 dose was a risk for admission due to FU-induced colitis (Odds ratio 1.30, 95% C.I. 1.12 - 1.50, P=0.0004). Conclusions: Hypoalbuminemia might constitute a marker of admission due to SAE. FU-induced colitis occurred in S-1 dose-related fashion, and the patients had lost their weight before appropriate course. It is suggested that clinicians should pay attention to patients’ weight loss during chemotherapy, notably time of initiation of chemotherapy.

scholarly journals Sildenafil for bronchopulmonary dysplasia and pulmonary hypertension: a meta-analysis

2019 ◽  
Vol 9 (3) ◽  
pp. 204589401983787 ◽  
Author(s):  
Marisa van der Graaf ◽  
Leonne Arindah Rojer ◽  
Willem Arnold Helbing ◽  
Irwin Karl Marcel Reiss ◽  
Jonathan Richard Gregory Etnel ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pulmonary Hypertension ◽  
Adverse Events ◽  
Preterm Infants ◽  
Bronchopulmonary Dysplasia ◽  
Complex Disease ◽  
Meta Analysis ◽  
Expression Patterns ◽  
Serious Adverse Events ◽  
Variable Expression

Bronchopulmonary dysplasia (BPD) is the most common complication in preterm infants and often complicated by pulmonary hypertension (PH), leading to substantial morbidity and mortality. Sildenafil is often used to treat PH and improve symptoms in this condition, even though evidence of safety and effectiveness is scarce. The aim of this study was to perform a systematic review and meta-analysis about the effectiveness and safety of chronic use of sildenafil in preterm infants with BPD-associated PH. Data sources were PubMed, EMBASE, and Medline. Studies reporting the effectiveness of sildenafil therapy in BPD-associated PH in newborns and infants were included. All-cause mortality, improvement in PH, improvement in respiratory scores, and adverse events were extracted. Five studies were included, yielding a total of 101 patients with 94.2 patient-years of total follow-up. The pooled mortality rate was 29.7%/year (95% confidence interval [CI] = 6.8–52.7). Estimated pulmonary arterial pressure improved > 20% in 69.3% (95% CI = 56.8–81.8) of patients within 1–6 months. Respiratory scores improved in 15.0% (95% CI = 0.0–30.4) of patients within 2–7 days. There were no serious adverse events during sildenafil therapy. This systematic review shows that in the treatment of BPD-associated PH in preterm infants, sildenafil may be associated with improvement in PAP and respiratory scores. However, there is no clear evidence of its effect on mortality rates. Considering BPD as a complex disease with variable expression patterns, these results support the need for a prospective registry and standardized approach.

scholarly journals Randomized controlled study of ECP with methoxsalen as first-line treatment of patients with moderate to severe cGVHD

2019 ◽  
Vol 3 (14) ◽  
pp. 2218-2229 ◽  
Author(s):  
Madan Jagasia ◽  
Christof Scheid ◽  
Gérard Socié ◽  
Francis Ayuketang Ayuk ◽  
Johanna Tischer ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase 1 ◽  
Standard Of Care ◽  
Response Assessment ◽  
Controlled Study ◽  
First Line ◽  
Serious Adverse Events ◽  
Hematopoietic Stem ◽  
Intention To Treat ◽  
First Line Therapy

Abstract The investigation of extracorporeal photopheresis (ECP) plus standard of care (SoC) (SoC+ECP) in chronic graft-versus-host disease (cGVHD) within prospective, randomized clinical studies is limited, despite its frequent clinical use. This phase 1/pilot study was the first randomized, prospective study to investigate ECP use as first-line therapy in cGVHD, based on the 2015 National Institutes of Health (NIH) consensus criteria for diagnosis and response assessment. Adult patients with new-onset (≤3 years of hematopoietic stem cell transplantation) moderate or severe cGVHD were randomized 1:1 to 26 weeks of SoC+ECP vs SoC (corticosteroids and cyclosporine A/tacrolimus) between 2011 and 2015. The primary endpoint was overall response rate (ORR), defined as complete or partial response, at week 28 in the intention-to-treat population (ITT). Other outcomes included quality of life (QoL) measures and safety. Sixty patients were randomized; ITT included 53 patients (SoC+ECP: 29; SoC: 24). Week 28 ORR was 74.1% (SoC+ECP) and 60.9% (SoC). Investigator-assessed ORR was 56.0% (SoC+ECP) and 66.7% (SoC). Patients treated with SoC experienced a decline in QoL over the 28-week study period; QoL remained unchanged in SoC+ECP patients. Most frequent treatment-emergent adverse events (TEAEs) in SoC+ECP patients were hypertension (31.0%), cough (20.7%), dyspnea (17.2%), and fatigue (17.2%). Seventeen patients (SoC+ECP: 8; SoC: 9) experienced 35 serious adverse events (SAEs). No TEAEs or SAEs were considered related to the ECP instrument or methoxsalen. The encouraging short-term results of this study could inform the design of subsequent studies. This trial was registered at www.clinicaltrials.gov as #NCT01380535.

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