901. MEDI8897 Prevents Serious RSV Disease in Healthy Preterm Infants

Abstract Background RSV is the principal cause of lower respiratory tract infection (LRTI) among infants, and a significant unmet need exists for RSV prevention in healthy infants. We have developed a highly potent, extended half-life monoclonal antibody (mAb), to protect infants for an entire RSV season using a single IM dose. Here we report the efficacy, safety, pharmacokinetics, and anti-drug antibody (ADA) responses for MEDI8897 in palivizumab-ineligible preterm infants born between 29 and 35 weeks gestation. Methods A total of 1,453 Infants were randomized 2:1 to receive a single 50 mg IM injection of MEDI8897 (n = 969) or placebo (n = 484) and followed for 360 days. Enrollment occurred just prior to the 2016 and 2017 RSV seasons in 23 northern and southern hemisphere countries. Blood was collected periodically. Infants with a medically attended (MA) LRTI (outpatient or inpatient) had nasal swabs obtained for central RSV testing by RT-PCR. Predefined clinical criteria were used for the case definition. Results A total of 1,417 (97.5%) subjects completed the 150-day efficacy follow-up period and 1,367 (94.1%) completed the study. In the MEDI8897 group, a 70.1% (95% CI: 52.3%, 81.2%; P < 0.0001) reduction in the incidence of medically attended RSV LRTI and a 78.4% (95% CI: 51.9%, 90.3%; P = 0.0002) reduction in the incidence of RSV LRTI hospitalization was achieved. These efficacy results were consistent when analyzed by hemisphere, RSV subtype, and subject demographics. Similar proportions of adverse events (86.8% placebo; 86.2% MEDI8897) and serious adverse events (16.9% placebo; 11.2% MEDI8897) were reported in study subjects. There were no significant hypersensitivity reactions with similar proportions reported for both groups (0.6% placebo; 0.5% MEDI8897). The incidence of ADA detected any time post baseline was low (3.8% placebo; 5.6% MEDI8897) with no impact on PK or safety. The occurrence of non-RSV LRTIs was similar for both groups indicating no replacement by other pathogens. Conclusion In this large randomized study of RSV prophylaxis in healthy preterm infants, MEDI8897 immunoprophylaxis provided a significant reduction in RSV MA-LRTI and hospitalization. These results have promising implications for the future of RSV prophylaxis for all infants. This study was funded by AstraZeneca and sanofi pasteur. Disclosures All Authors: No reported Disclosures.

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Efficacy of Phenazone in the Treatment of Acute Migraine Attacks: A Double-Blind, Placebo-Controlled, Randomized Study

Cephalalgia ◽

10.1111/j.1468-2982.2004.00764.x ◽

2004 ◽

Vol 24 (10) ◽

pp. 888-893 ◽

Cited By ~ 15

Author(s):

H Göbel ◽

A Heinze ◽

U Niederberger ◽

T Witt ◽

V Zumbroich

Keyword(s):

Adverse Events ◽

Randomized Study ◽

Controlled Study ◽

Acute Migraine ◽

Serious Adverse Events ◽

Double Blind ◽

Double Blind Placebo ◽

Number Of Patients ◽

Significant Difference ◽

Main Target

In this study we compared the efficacy of 1000 mg phenazone with that of placebo in the treatment of acute migraine attacks in a randomized double-blind, placebo-controlled study of 208 patients. The main target criterion was the number of patients with a pain reduction from severe or moderate to slight or no pain 2 h after taking the pain medication. The percentage of patients satisfying the main target criterion was 48.6% for phenazone and 27.2% ( P < 0.05) for placebo. Freedom from pain after 2 h was reported by 27.6% with phenazone treatment and 13.6% ( P < 0.05) with placebo. Compared with placebo, the phenazone treatment also resulted in a significant improvement in the associated migraine symptoms of nausea, phonophobia and photophobia. Of patients treated with phenazone 11.4%, and 5.8% of those treated with placebo reported adverse events. There was no significant difference between the groups with regard to numbers of patients with adverse events. No serious adverse events occurred. The results show that phenazone at a dosage of 1000 mg is effective and well tolerated in the treatment of acute migraine attacks.

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Feasibility of Non-Anesthesiologist-Administered Propofol Sedation for Emergency Endoscopic Retrograde Cholangiopancreatography

Gastroenterology Research and Practice ◽

10.1155/2015/685476 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Nobuhito Ikeuchi ◽

Takao Itoi ◽

Takuji Gotoda ◽

Chika Kusano ◽

Shin Kono ◽

...

Keyword(s):

Adverse Events ◽

Endoscopic Retrograde Cholangiopancreatography ◽

Acute Cholangitis ◽

Careful Monitoring ◽

Endoscopic Retrograde ◽

Serious Adverse Events ◽

Significant Difference ◽

Group A ◽

Group B ◽

Technical Safety

Background. The safety of non-anesthesiologist-administered propofol (NAAP) sedation in emergent endoscopic retrograde cholangiopancreatography (ERCP) has not been fully clarified. Thus, the aim of this study was to assess the safety of NAAP sedation in emergent ERCP.Materials and Methods. We retrospectively analyzed 182 consecutive patients who had obstructive jaundice and who underwent ERCP under NAAP sedation. The patients were divided into Group A (with mild acute cholangitis or without acute cholangitis) and Group B (moderate or severe acute cholangitis). And technical safety and adverse events were assessed.Results. The adverse events were hypoxia (31 cases), hypotension (26 cases), and bradycardia (2 cases). There was no significant difference in the rate of each adverse event of hypoxia and bradycardia in either group. Although the rate of transient hypotension associated in Group B was higher than that in Group A, it was immediately improved with conservative treatment. Moreover, there were no patients who showed delayed awakening, or who developed other complications.Conclusions. In conclusion, NAAP sedation is feasible even in emergent ERCP. Although some transient adverse events (e.g., hypotension) were observed, no serious adverse events occurred. Thus, propofol can be used in emergent ERCP but careful monitoring is mandatory.

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Use of Nanotechnology-Designed Footsock in the Management of Preulcerative Conditions in the Diabetic Foot: Results of a Single, Blind Randomized Study

The International Journal of Lower Extremity Wounds ◽

10.1177/1534734608318138 ◽

2008 ◽

Vol 7 (2) ◽

pp. 82-87 ◽

Cited By ~ 9

Author(s):

Banchellini Elisa ◽

Macchiarini Silvia ◽

Dini Valentina ◽

Rizzo Loredana ◽

Tedeschi Anna ◽

...

Keyword(s):

Treatment Group ◽

Adverse Events ◽

Water Loss ◽

Diabetic Foot ◽

Randomized Study ◽

Clinical Score ◽

Transepidermal Water Loss ◽

Group A ◽

Group B ◽

Single Blind

The Difoprev system constituted by a sock loaded with nanocapsules containing a hydrating agent in the diabetic foot is tested. A total of 30 neuropathic outpatients with foot anhydrosis were randomized into group A, treated with the application of the sock with the nanocapsules, and group B wearing only the socks without the nanocapsules. Patients were blindly evaluated with a clinical score, hygrometry, transepidermal water loss, skin temperature, and skin hardness at baseline and after 6 weeks. No difference between the groups emerged at baseline. Although group B showed no changes at the end of the treatment, group A significantly ( P < .05) improved in all the parameters evaluated. No adverse events were recorded in both groups during the study. The use of hydrating agents carried by nanocapsules-loaded socks is safe and effective for the neuropathic diabetic foot.

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Proposal for a new therapeutic high dosage of Pidotimod in children with Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome: an observational study.

10.21203/rs.3.rs-25144/v1 ◽

2020 ◽

Author(s):

Sara Manti ◽

Federica Filosco ◽

Giuseppe Fabio Parisi ◽

Giuseppe Germano Finocchiaro ◽

Maria Papale ◽

...

Keyword(s):

Adverse Events ◽

Periodic Fever ◽

Phase 1 ◽

Aphthous Stomatitis ◽

Potential Treatment ◽

Phase 2 ◽

Serious Adverse Events ◽

Group A ◽

Pfapa Syndrome ◽

Group B

Abstract Background. Despite to PFAPA syndrome is considered a benign and self-limited condition in childhood its impact on patients and families can be remarkable in many cases. Currently, the therapeutic options for managing are non-specific and no consensus exists about the best treatment to use. Pidotimod has been suggested as a new potential treatment in PFAPA syndrome for its immunodulatory effects. We conducted a preliminary, prospective, controlled, open, cross-over trial to assess the efficacy and the safety of Pidotimod in the treatment of children with PFAPA syndrome.Methods. 22 children with PFAPA syndrome were randomly allocated to treatment with Pidotimod (with 2 vials of 400 mg daily) in combination with betamethasone 0.5-1 mg on need (group A) or betamethasone 0.5-1 mg on need (group B). Each treatment period was for 3 months (Phase 1), after that patients were switched to the other arm for other 3 months (Phase 2). Efficacy was expressed in terms of number of episodes of fever, tonsillitis, and aphthous stomatitis, as well as the additional use of betamethasone on need. Safety and tolerability of the Pidotimod were evaluated on the basis of the number and type of adverse events (AEs) recorded during the treatment.Results. Patients receiving Pidotimod and betametasone showed a significant decrease in frequency of fevers (p = 0.002); number of episodes of tonsillitis (p = 0.049); aphthous stomatitis (p = 0.036) as well as the betamethasone use on need (p = 0.007). Overall, 19/22 (86.4%) showed benefits from Pidotimod administration. The safety profile of Pidotimod was excellent as no serious adverse events have been reported in the treated groups.Conclusions. We firstly showed that high dosage of Pidotimod is an effective and safe to reduce the PFAPA attacks in children.

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Proposal for a new therapeutic high dosage of Pidotimod in children with Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome: an interventional study.

10.21203/rs.3.rs-25144/v2 ◽

2020 ◽

Author(s):

Sara Manti ◽

Federica Filosco ◽

Giuseppe Fabio Parisi ◽

Giuseppe Germano Finocchiaro ◽

Maria Papale ◽

...

Keyword(s):

Adverse Events ◽

Periodic Fever ◽

Phase 1 ◽

Aphthous Stomatitis ◽

Interventional Study ◽

Serious Adverse Events ◽

Group A ◽

Pfapa Syndrome ◽

Decision Group ◽

Group B

Abstract Background. Despite to PFAPA syndrome is considered a benign and self-limited condition in childhood its impact on patients and families can be remarkable in many cases. Currently, the therapeutic options for managing are non-specific and no consensus exists about the best treatment to use. Pidotimod has been suggested as a new potential treatment in PFAPA syndrome for its immunodulatory effects. We conducted a preliminary, prospective, controlled, open, cross-over trial to assess the efficacy and the safety of Pidotimod in the treatment of children with PFAPA syndrome. Methods. 22 children with PFAPA syndrome were randomly allocated to treatment with pidotimod (with 2 vials of 400mg daily) in combination with betamethasone 0.5-1 mg on need, based on parents/caregivers' decision (group A) or betamethasone 0.5-1mg on need, based on parents/caregivers' decision (group B). Each treatment period was for 3 months (Phase 1), after that patients were switched to the other arm for other 3 months (Phase 2). Efficacy was expressed in terms of number of episodes of fever, pharyngitis, or aphthous stomatitis, as well as the additional use of betamethasone on need. Safety and tolerability of the Pidotimod were evaluated on the basis of the number and type of adverse events (AEs) recorded during the treatment.Results. Patients receiving Pidotimod and use betametasone showed a significant decrease in frequency of fevers (p=0.002); number of episodes of pharyngitis (p=0.049); aphthous stomatitis (p=0.036) as well as the betamethasone use on need (p=0.007). Overall, 19/22 (86.4%) showed benefits from Pidotimod administration. The safety profile of Pidotimod was excellent as no serious adverse events have been reported in the treated groups.Conclusions. We firstly showed that high dosage of Pidotimod could be an effective and safe to reduce the PFAPA attacks in children.

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Patients’ and rheumatologists’ perspectives on the efficacy and safety of low-dose glucocorticoids in rheumatoid arthritis—an international survey within the GLORIA study

Rheumatology ◽

10.1093/rheumatology/keaa785 ◽

2021 ◽

Author(s):

T Santiago ◽

M Voshaar ◽

M de Wit ◽

P D Carvalho ◽

F Buttgereit ◽

...

Keyword(s):

Adverse Events ◽

Health Professionals ◽

Low Dose ◽

Unmet Need ◽

Signs And Symptoms ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

The Real ◽

Patient Organizations ◽

Published Evidence

Abstract Objective To evaluate the current perspectives of patients and health professionals regarding the efficacy and safety of low-dose glucocorticoids (GCs) in RA. Methods Two online surveys were disseminated to patients and health professionals, in their native language, through national patient organizations and national rheumatology medical societies, respectively. SurveyMonkey®, MediGuard.org and the Glucocorticoid Low-dose Outcome in RA Study (GLORIA) website were used to offer and deliver these surveys. Results A total of 1221 RA patients with exposure to GCs, and 414 rheumatologists completed the surveys. Patients and rheumatologists reported high levels of agreement regarding the efficacy of low-dose GCs: at least 70% considered that they are very rapid and effective in the control of signs and symptoms of RA. However, half of the patients also reported having suffered serious adverse events with GCs, and 83% described concerns about safety. The majority of rheumatologists estimated that endocrine, ophthalmologic and cutaneous adverse events affect >4% of all patients treated with low-dose GCs for 2 years, based on a heat map. Conclusions RA patients with self-reported exposure to GCs express high levels of satisfaction with low-dose GCs efficacy, as do rheumatologists. However, both expressed excessive concerns regarding the safety of GCs (greatly exceeding the published evidence data), which may compromise the optimal use of this medication. This study indicates that there is an unmet need for appropriately designed prospective trials that shed light on the real risk associated with low-dose GCs, as well as a need for renovated educational programs on the real benefits and harms of low-dose GCs, for both patients and physicians.

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Transfusion with Washed vs. Unwashed Packed Red Cells in Coronary Artery Bypass Graft (CABG) Surgery: Major Outcome Differences

Blood ◽

10.1182/blood.v124.21.2887.2887 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2887-2887 ◽

Cited By ~ 1

Author(s):

Wenche Jy ◽

Orlando Gomez-Marin ◽

Tomas A Salerno ◽

Anthony Panos ◽

Donald Williams ◽

...

Keyword(s):

Adverse Events ◽

Artery Bypass ◽

Randomized Study ◽

Bypass Graft ◽

Surgical Patients ◽

Prospective Randomized Study ◽

Artery Bypass Graft ◽

Serious Adverse Events ◽

Small Patient Population ◽

Small Patient

Abstract BACKGROUND: Blood transfusion (Tx) carries greater risks of adverse events (AEs) than previously appreciated. These adverse effects include higher incidence of post-surgical infections, longer hospital stay, higher mortality, more frequent serious adverse events (SAE’s), and generally poorer surgical outcomes. Accordingly, ameliorating these adverse effects constitutes an urgent challenge to medical science. Factors responsible for Tx-related adverse events (AE’s) are not well understood. Many potentially toxic substances are released during blood storage, and many of them have been implicated or postulated as culprits. Washing of packed RBC remove these products and may ameliorate transfusion-related AE’s. Benefits of washed RBC are well established for pediatric surgical patients, chiefly by preventing hyperkalemia, but use of washed RBC in adult surgical patients has not heretofore been systematically investigated. We here report results of a prospective randomized study directly comparing surgical outcomes, in terms of mortality and AE’s, between groups of adult CABG patients transfused with either washed or unwashed (conventional) RBC. METHODS: A prospective randomized study of 148 patients undergoing coronary artery bypass graft (CABG) was conducted. Fifty-eight patients were randomized to receive unwashed (conventional) RBC (UW group) and 41 to washed RBC (W group). The remaining 49 did not require Tx. The main in-hospital outcomes recorded included mortality, serious adverse events (SAE’s), non-serious adverse events (AE’s), and SOFA scores pre- and post-surgery. A telephone interview was conducted at day 30 post-discharge, and mortality at one-year was also assessed. The statistical techniques used for the comparison of the UW and W RBC groups included: independent sample t-tests for variables with normal or approximately normal distribution; Mann-Whitney tests for variables with skewed distributions and for ordinal variables; chi-squared tests or Fisher’s exact tests for discrete variables; and logistic regression model for assessing different factors as predictors of the occurrence of each kind of event. RESULTS: Between the 2 groups, demographic, clinical, and comorbidity data were similar and there was no statistically significant difference in number of serious AE’s (SAE’s). However, 4 of 6 patients died from SAE’s in the UW group but all 7of 7 with SAE in the W group survived. The in-hospital mortality was greater in the UW group (4 vs. 0, p = 0.149) but 1-year post-op mortality was significantly higher in UW group (7 vs. 0, p=0.036). Frequency of less serious AE’s was higher in UW group in every category. Negative binomial regression analyses showed that, after adjusting for comorbidities, UW-group are likely to experience 64% more AEs (p= 0.027). The 30-day follow-up showed similar trends of higher AE’s in UW-group, but only CNS-related AE’s were significant (30 vs. 5, p<0.01). CONCLUSIONS / DISCUSSION: These data suggest major benefits to patient outcomes by use of washed RBC in CABG. Most important is significant reduction of mortality. Less serious AE’s were also lower in the W group in nearly every category, but only CNS-related AE’s were statistically significant in this comparatively small patient population. To our knowledge, this is the first prospective randomized study in adults to assess possible benefits of washing RBC prior to cardiac surgery. At present, washed RBCs are seldom used in adults but the present study clearly demonstrates major advantages. It may be possible to reduce costs of washing by using on-site cell call-salvage equipment but this needs to be evaluated. This study was undertaken with the hypothesis that cell-derived microparticles (MP) are major culprits in Tx-associated AE’s. Further study is needed to determine if that hypothesis is correct. Other evidence has led us to conjecture that MP are largely responsible for post-surgical adverse outcomes; the present study is consistent with that conjecture but does not prove it. A major shortcoming of this study is the comparatively small patient population. A much larger study, including other types of surgery, is certainly warranted by these findings, and should be designed to include more quantitative evaluation of post-surgical cognitive impairment. Disclosures No relevant conflicts of interest to declare.

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Efficacy, safety, and lot to lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): a double-blind, randomised, controlled phase 3 trial

10.1101/2021.06.30.21259439 ◽

2021 ◽

Author(s):

Raches Ella ◽

Siddharth Reddy ◽

William Blackwelder ◽

Varsha Potdar ◽

Pragya Yadav ◽

...

Keyword(s):

Adverse Events ◽

Vaccine Efficacy ◽

Severe Disease ◽

Case Definition ◽

Phase 3 ◽

Serious Adverse Events ◽

Double Blind ◽

Multicentre Phase ◽

Randomised Controlled ◽

Placebo Recipients

Background: We report the clinical efficacy against COVID 19 infection of BBV152, a whole virion inactivated SARS CoV 2 vaccine formulated with a Toll like receptor 7/8 agonist molecule adsorbed to alum (Algel IMDG). Methods: We did a double-blind, randomised, multicentre, phase 3 clinical trial in 25 Indian hospitals to evaluate the efficacy, safety, and immunological lot consistency of BBV152. Healthy adults (age 18 to 98 years) randomised 1:1 using a sponsor-supplied randomisation scheme received two intramuscular doses of vaccine or placebo administered four weeks apart. The primary outcome was laboratory confirmed symptomatic COVID 19, occurring at least 14 days after the second dose. Secondary outcomes were efficacy in subgroups for age (18 to < 60 years and >=60 years) and in participants with pre-existing stable medical conditions. We also evaluated safety, reactogenicity, and consistency of immune responses for three consecutive manufacturing lots. Findings: Between November 16, 2020 and January 7, 2021 we recruited 25,798 participants who were randomised to BBV152 or placebo groups; 24,419 received two doses of BBV152 (n = 12,221) or placebo (n = 12,198). In a case-driven analysis, 130 cases of symptomatic COVID-19 were reported in 16,973 (0.77%) participants with follow-up at least two weeks after the second vaccination; 24 occurred in the vaccine group and 106 in placebo recipients giving an overall vaccine efficacy of 77.8% (95% CI: 65.2,86.4). Sixteen cases, one vaccinee and 15 placebo recipients, met the severe symptomatic COVID-19 case definition giving a vaccine efficacy of 93.4% (57.1,99.8). Efficacy against asymptomatic COVID 19 was 63.6% (29.0, 82.4). BBV152 conferred 65.2% (95% CI: 33.1, 83.0) protection against the SARS CoV 2 Variant of Concern, B.1.617.2 (Delta). BBV152 was well tolerated with no clinically or statistically significant differences in the distributions of solicited, unsolicited, or serious adverse events between vaccine and placebo groups. No cases of anaphylaxis or vaccine-related deaths were reported. Interpretation: BBV152 was immunogenic and highly efficacious against symptomatic and asymptomatic COVID 19 variant associated disease, particularly against severe disease in adults. Vaccination was well tolerated with an overall incidence of adverse events observed over a median of 146 days that was lower than that observed with other COVID-19 vaccines.

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Proposal for a new therapeutic high dosage of Pidotimod in children with Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome: a randomized controlled study.

10.21203/rs.3.rs-25144/v3 ◽

2020 ◽

Author(s):

Sara Manti ◽

Federica Filosco ◽

Giuseppe Fabio Parisi ◽

Giuseppe Germano Finocchiaro ◽

Maria Papale ◽

...

Keyword(s):

Adverse Events ◽

Periodic Fever ◽

Phase 1 ◽

Aphthous Stomatitis ◽

Controlled Study ◽

Serious Adverse Events ◽

Group A ◽

Pfapa Syndrome ◽

Decision Group ◽

Group B

Abstract Background. Despite to PFAPA syndrome is considered a benign and self-limited condition in childhood its impact on patients and families can be remarkable in many cases. Currently, the therapeutic options for managing are non-specific and no consensus exists about the best treatment to use. Pidotimod has been suggested as a new potential treatment in PFAPA syndrome for its immunodulatory effects. We conducted a preliminary, prospective, controlled, open, cross-over trial to assess the efficacy and the safety of Pidotimod in the treatment of children with PFAPA syndrome. Methods. 22 children with PFAPA syndrome were randomly allocated to treatment with pidotimod (with 2 vials of 400mg daily) in combination with betamethasone 0.5-1 mg on need, based on parents/caregivers' decision (group A) or betamethasone 0.5-1mg on need, based on parents/caregivers' decision (group B). Each treatment period was for 3 months (Phase 1), after that patients were switched to the other arm for other 3 months (Phase 2). Efficacy was expressed in terms of number of episodes of fever, pharyngitis, or aphthous stomatitis, as well as the additional use of betamethasone on need. Safety and tolerability of the Pidotimod were evaluated on the basis of the number and type of adverse events (AEs) recorded during the treatment.Results. Patients receiving Pidotimod and use betametasone showed a significant decrease in frequency of fevers (p=0.002); number of episodes of pharyngitis (p=0.049); aphthous stomatitis (p=0.036) as well as the betamethasone use on need (p=0.007). Overall, 19/22 (86.4%) showed benefits from Pidotimod administration. The safety profile of Pidotimod was excellent as no serious adverse events have been reported in the treated groups.Conclusions. We firstly showed that high dosage of Pidotimod could be an effective and safe to reduce the PFAPA attacks in children.

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

Pulmonary Circulation ◽

10.1177/2045894019837875 ◽

2019 ◽

Vol 9 (3) ◽

pp. 204589401983787 ◽

Cited By ~ 6

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.

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