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1.
Trials ; 23(1): 302, 2022 Apr 12.
Article in English | MEDLINE | ID: covidwho-1789128

ABSTRACT

BACKGROUND: Proton-pump inhibitors (PPI) are liberally prescribed in patients with liver cirrhosis. Observational studies link PPI therapy in cirrhotic patients with an increased risk for infectious complications, hepatic encephalopathy and an increased risk for hospitalization and mortality. However, patients with liver cirrhosis are also considered to be at risk for peptic ulcer bleeding. The STOPPIT trial evaluates if discontinuation of a pre-existing PPI treatment delays a composite endpoint of re-hospitalization and/or death in patients (recently) hospitalized with liver cirrhosis compared to patients on continued PPI medication. METHODS: The STOPPIT-trial is a prospective, multicentre, randomized, double-blinded, placebo-controlled, parallel-group trial. In total, 476 patients with complicated liver cirrhosis who already receive long-term PPI therapy without evidence-based indication are 1:1 randomized to receive either esomeprazole 20 mg (control group) or placebo (intervention group) for 360 days. Patients with an indication for PPI therapy (such as a recent diagnosis of peptic ulcers, severe reflux esophagitis, severe hemorrhagic gastritis, recent endoscopic therapy for oesophageal varices) are excluded. The primary composite endpoint is the time-to re-hospitalization and/or death. Secondary endpoints include rates of re-hospitalization, mortality, occurrence of infections, hepatic decompensation and acute-on-chronic liver failure. The safety endpoint is defined as manifestation of an evidence-based indication for PPI re-therapy. The impact of PPI continuation or discontinuation on the intestinal microbiota will be studied. The recruitment will take place at 18 study sites throughout Germany. Recruitment has started in April 2021. DISCUSSION: The STOPPIT trial is the first clinical trial to study the effects of PPI withdrawal on relevant outcome variables in patients with complicated liver cirrhosis. If the hypothesis that PPI withdrawal improves clinical outcomes of cirrhosis patients is confirmed, this would argue for a strong restriction of the currently liberal prescription practice of PPIs in this population. If, on the other hand, the trial demonstrates an increased risk of gastrointestinal bleeding events in patients after PPI withdrawal, this could create a rationale for a more liberal, prophylactic PPI treatment in patients with liver cirrhosis. TRIAL REGISTRATION: EU clinical trials register EudraCT 2019-005008-16 (registered December 27, 2019). CLINICALTRIALS: gov NCT04448028 (registered June 25, 2020). German Clinical Trials Register DRKS00021290 (registered March 10, 2021).


Subject(s)
COVID-19 , Proton Pump Inhibitors , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Liver Cirrhosis/drug therapy , Multicenter Studies as Topic , Prospective Studies , Proton Pump Inhibitors/adverse effects , Randomized Controlled Trials as Topic , SARS-CoV-2
2.
Br J Clin Pharmacol ; 88(5): 2452-2453, 2022 May.
Article in English | MEDLINE | ID: covidwho-1788831
3.
J Glob Health ; 12: 05005, 2022.
Article in English | MEDLINE | ID: covidwho-1699578

ABSTRACT

Background: The adverse effects of proton pump inhibitors (PPIs) on pneumonia have been well reported. However, the relationship between the use of PPIs and the adverse outcomes of coronavirus disease 2019 (COVID-19) is currently inconclusive. In this study, we aimed to explore the relationship between the use of PPIs and the in-hospital mortality among patients who were laboratory-confirmed SARS-CoV-2. Methods: Data was derived from 2 hospitals which both were the first batch of SARS-CoV-2 specialist hospitals with four types of sensitivity analyses. This cohort included 4634 patients older than 18 years who were laboratory-confirmed SARS-CoV-2. Endpoints were death in hospital (primary) and the recovery of COVID-19 (secondary: the time of COVID-19 nucleic acid testing turning negative). Results: In the entire cohort, there were 3588 non-users, 399 ≤ 0.5 defined daily dose (DDD) PPIs users, 483 1 DDD users, and 164 ≥ 1.5 DDD users. The multivariate logistic regression analysis (odds ratio (OR) = 3.63, 95% confidence interval (CI) = 1.83-7.23, P = 0.0002) and four types of sensitivity analyses showed higher mortality in patients using PPIs during hospitalization, while the relationship between different PPIs dosages and the hospital mortality remained insignificant. Usage of the PPIs significantly prolongs the time of COVID-19 nucleic acid testing turning negative. Conclusions: The use of PPIs may increase the risk of in-hospital death of patients who were laboratory-confirmed SARS-CoV-2, which means that physicians may need to re-evaluate the benefit-risk assessment of the use of PPIs during the COVID-19 pandemic.


Subject(s)
COVID-19 , COVID-19 Testing , Hospital Mortality , Humans , Pandemics , Proton Pump Inhibitors/adverse effects , SARS-CoV-2
4.
Eur J Gastroenterol Hepatol ; 34(2): 137-141, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1672393

ABSTRACT

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 may escape the inactivation by gastric acid because of hypochlorhydria caused by proton pump inhibitors (PPIs), which could predispose the patients to severe COVID-19. METHODS: We studied the association between prehospitalization PPI exposure and clinical outcomes among hospitalized COVID-19 patients. RESULTS: A total of 295 hospitalized COVID-19 patients were included in the study. 15.6% of hospitalized COVID-19 patients were on PPIs at home. Mortality among PPI-users was 2.3 times higher than non-users, along with 2.3 times higher risk of acute respiratory distress syndrome after adjusting for confounding variables. CONCLUSION: We found that prehospitalization PPI-exposure is independently associated with worse clinical outcomes, including mortality in COVID-19 patients, regardless of the presence of cardiovascular comorbidities.


Subject(s)
COVID-19 , Proton Pump Inhibitors , Hospitalization , Humans , Proton Pump Inhibitors/adverse effects , SARS-CoV-2
5.
Jpn J Infect Dis ; 75(1): 10-15, 2022 Jan 24.
Article in English | MEDLINE | ID: covidwho-1649030

ABSTRACT

The findings of previous research on the association between proton pump inhibitor (PPI) use and the treatment and prevention of coronavirus disease 2019 (COVID-19) are inconsistent. Therefore, this meta-analysis was conducted to clarify the outcomes of patients taking PPIs. This analysis included 14 articles with more than 268,683 subjects. PPI use was not associated with increased or decreased risk of COVID-19 infection (odds ratio [OR] 1.64, 95% confidence interval [CI] = 0.54-5.00, P = 0.39) or mortality (OR = 1.91, 95% CI = 0.86-4.24, P = 0.11). However, PPI use increased the risks of severe disease (OR 1.67, 95% CI = 1.37-2.02, P < 0.00001) and secondary infection (OR 4.62, 95% CI = 2.55-8.39, P < 0.00001). In summary, PPI use was not associated with an increased risk of infection and mortality in COVID-19 but appeared to be associated with an increased risk of progression to severe disease and secondary infection. However, more original studies are urgently needed to further clarify the relationship between PPI use and COVID-19.


Subject(s)
COVID-19 , Proton Pump Inhibitors , Humans , Proton Pump Inhibitors/adverse effects , SARS-CoV-2
8.
Monaldi Arch Chest Dis ; 91(4)2021 Oct 19.
Article in English | MEDLINE | ID: covidwho-1478189

ABSTRACT

Identification of risk factors for severe outcome of SARS-CoV-2 infection is an important issue in COVID-19 management. Much attention has been focused on comorbidities as well as drugs taken by patients. Usage of proton pump inhibitors (PPIs) appears to potentially influence disease course. These drugs are known to reduce stomach acid and also modulate the immune system. Their use, prior to and during COVID-19 infection, seems to predispose to the development of more severe pneumonia and therefore to a greater risk of mortality. Instead, the use of histamine receptor 2 antagonists (H2RAs) seems to be associated with a better outcome in patients with COVID-19, in terms of symptoms, risk of intubation and death. As PPIs are essential for treatment of many disorders, usage of these drugs should be balanced considering the benefits and risk ratio, in order to guarantee their correct use for the necessary time. It remains to be clarified whether the detrimental effects, in terms of COVID-19 severe outcome, are due to PPIs or to the underlying disease for which they are administered. New controlled-randomized trials are required to better understand their impact in SARS-CoV-2 infections. *Vanvitelli/Monaldi COVID Group: Adriano Cristinziano, Carolina Delle Donne, Cecilia Calabrese, Fabio Perrotta, Filippo Scialò, Francesco Lassandro, Gennaro Mazzarella, Giorgio Paoli, Leonardo De Luca, Maria Galdo, Miriam Buonincontro, Roberta Cianci, Rosalba Donizzetti, Stefano Sanduzzi Zamparelli, Tullio Valente, Vito D'Agnano, Vittorio Bisogni.


Subject(s)
COVID-19 , Proton Pump Inhibitors , Humans , Proton Pump Inhibitors/adverse effects , Risk Factors , SARS-CoV-2
9.
Br J Clin Pharmacol ; 88(4): 1551-1566, 2022 02.
Article in English | MEDLINE | ID: covidwho-1462736

ABSTRACT

AIMS: The aim was to perform an umbrella review to summarise the existing evidence on proton-pump inhibitor (PPI) use and adverse outcomes and to grade the certainty of evidence. METHODS: Electronic databases were searched up to July 2021 for meta-analyses of cohort studies and/or randomised controlled trials (RCTs). Summary effect sizes from a random-effects model, between-study heterogeneity, 95% prediction interval, small-study effect, excess significance and credibility ceilings were devised to classify the credibility of evidence from meta-analyses of cohort studies, whereas the GRADE approach was used for meta-analyses of RCTs. RESULTS: In meta-analyses of cohort studies, 52 of the 91 examined associations were statistically significant (P ≤ .05). Convincing evidence emerged from main analysis for the association between PPI use and risk of all-site fracture and chronic kidney disease in the elderly population. However, none of these associations remained supported by convincing evidence after sensitivity analyses. The use of PPI is also associated with an increased risk of mortality due to COVID-19 infection and other related adverse outcomes, but the quality of evidence was weak. In meta-analyses of RCTs, 38 of the 63 examined associations were statistically significant. However, no associations were supported by high or moderate-quality evidence. CONCLUSION: This study's findings imply that most putative adverse outcomes associated with PPI use may not be supported by high-quality evidence and are likely to have been affected by underlying confounding factors. Future research is needed to confirm the causal association between PPI use and risk of fracture and chronic kidney disease.


Subject(s)
COVID-19 , Renal Insufficiency, Chronic , Aged , Cohort Studies , Humans , Meta-Analysis as Topic , Proton Pump Inhibitors/adverse effects , Randomized Controlled Trials as Topic
12.
Clin Gastroenterol Hepatol ; 20(1): 247-248, 2022 01.
Article in English | MEDLINE | ID: covidwho-1351573
13.
Turk J Med Sci ; 51(3): 1675-1681, 2021 08 30.
Article in English | MEDLINE | ID: covidwho-1264581

ABSTRACT

Background and aim: The aim of this study is to evaluate whether the long-term (≥4 weeks) use of proton pump inhibitors (PPIs) is a risk factor for intubation requirement and mortality in patients hospitalized for COVID-19. Materials and methods: In this multicentric retrospective study, a total of 382 adult patients (≥18 years of age) with confirmed COVID-19 who were hospitalized for treatment were enrolled. The patients were divided into two groups according to the periods during which they used PPIs: the first group included patients who were not on PPI treatment, and the second group included those who have used PPIs for more than 4 weeks. Results: The study participants were grouped according to their PPI usage history over the last 6 months. In total, 291 patients did not use any type of PPI over the last 6 months, and 91 patients used PPIs for more than 4 weeks. Older age (HR: 1.047, 95% CI: 1.026­1.068), current smoking (HR: 2.590, 95% CI: 1.334­5.025), and PPI therapy for more than 4 weeks (HR: 1.83, 95% CI: 1.06­2.41) were found to be independent risk factors for mortality. Conclusion: The results obtained in this study show that using PPIs for more than 4 weeks is associated with negative outcomes for patients with COVID-19. Patients receiving PPI therapy should be evaluated more carefully if they are hospitalized for COVID-19 treatment.


Subject(s)
COVID-19/mortality , Proton Pump Inhibitors/adverse effects , Adult , Aged , Female , Humans , Intubation, Intratracheal/statistics & numerical data , Male , Middle Aged , Retrospective Studies , Risk Factors , SARS-CoV-2 , Time , Turkey/epidemiology
14.
Am J Gastroenterol ; 116(8): 1638-1645, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1248431

ABSTRACT

INTRODUCTION: Proton pump inhibitor (PPI) use was recently reported to be associated with increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and worse clinical outcomes. The underlying mechanism(s) for this association are unclear. METHODS: We performed a prospective study of hospitalized coronavirus disease 2019 (COVID-19) patients and COVID-negative controls to understand how PPI use may affect angiotensin-converting enzyme 2 (ACE2) expression and stool SARS-CoV-2 RNA. Analysis of a retrospective cohort of hospitalized patients with COVID-19 from March 15, 2020 to August 15, 2020 in 6 hospitals was performed to evaluate the association of PPI use and mortality. Covariates with clinical relevance to COVID-19 outcomes were included to determine predictors of in-hospital mortality. RESULTS: Control PPI users had higher salivary ACE2 mRNA levels than nonusers, 2.39 ± 1.15 vs 1.22 ± 0.92 (P = 0.02), respectively. Salivary ACE2 levels and stool SARS-CoV-2 RNA detection rates were comparable between users and nonusers of PPI. In 694 hospitalized patients with COVID-19 (age = 58 years, 46% men, and 65% black), mortality rate in PPI users and nonusers was 30% (68/227) vs 12.1% (53/439), respectively. Predictors of mortality by logistic regression were PPI use (adjusted odds ratio [aOR] = 2.72, P < 0.001), age (aOR = 1.66 per decade, P < 0.001), race (aOR = 3.03, P = 0.002), cancer (aOR = 2.22, P = 0.008), and diabetes (aOR = 1.95, P = 0.003). The PPI-associated mortality risk was higher in black patients (aOR = 4.16, 95% confidence interval: 2.28-7.59) than others (aOR = 1.62, 95% confidence interval: 0.82-3.19, P = 0.04 for interaction). DISCUSSION: COVID-negative PPI users had higher salivary ACE2 expression. PPI use was associated with increased mortality risk in patients with COVID-19, particularly African Americans.


Subject(s)
Angiotensin-Converting Enzyme 2/blood , COVID-19/blood , COVID-19/mortality , Proton Pump Inhibitors/adverse effects , Adult , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies , Risk Assessment
15.
Clin Gastroenterol Hepatol ; 19(9): 1845-1854.e6, 2021 09.
Article in English | MEDLINE | ID: covidwho-1225170

ABSTRACT

BACKGROUND & AIMS: Proton pump inhibitor (PPI) use has been associated with increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe outcomes. However, meta-analyses show unclear results, leading to uncertainty regarding the safety of PPI use during the ongoing coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted a nationwide observational study including all SARS-CoV-2 cases (n = 83,224) in Denmark as of December 1, 2020. The association of current PPI use with risk of infection was examined in a case-control design. We investigated the risk of severe outcomes, including mechanical ventilation, intensive care unit admission, or death, in current PPI users (n = 4473) compared with never users. Propensity score matching was applied to control for confounding. Finally, we performed an updated meta-analysis on risk of SARS-CoV-2 infection and COVID-19 mortality attributable to PPI use. RESULTS: Current PPI use was associated with increased risk of infection; adjusted odds ratio, 1.08 (95% confidence interval [CI], 1.03-1.13). Among SARS-CoV-2 cases, PPI use was associated with increased risk of hospital admission; adjusted relative risk, 1.13 (1.03-1.24), but not with other severe outcomes. The updated meta-analysis showed no association between PPI use and risk of infection or mortality; pooled odds ratio, 1.00 (95% CI, 0.75-1.32) and relative risk, 1.33 (95% CI, 0.71-2.48). CONCLUSIONS: Current PPI use may be associated with an increased risk of SARS-CoV-2 infection and hospital admission, but these results with minimally elevated estimates are most likely subject to residual confounding. No association was found for severe outcomes. The results from the meta-analysis indicated no impact of current PPI use on COVID-19 outcomes.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Observational Studies as Topic , Pandemics , Proton Pump Inhibitors/adverse effects , Respiration, Artificial
16.
Pharmacol Rep ; 73(6): 1642-1649, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1174060

ABSTRACT

BACKGROUND: The negative impacts of proton pump inhibitor (PPI), including the risk of pneumonia and mortality, have been reported previously. This meta-analysis aimed to address the current interest of whether the administration of PPI could increase the susceptibility and risk of poor outcome in COVID-19. METHODS: We performed a systematic literature search from PubMed, Embase, EBSCOhost, and EuropePMC databases up until 3 December 2020. The main outcome was composite poor outcome which comprised of mortality and severe COVID-19. Severe COVID-19 in this study was defined as patients with COVID-19 that fulfill the criteria for severe CAP, including the need for intensive unit care or mechanical ventilation. The secondary outcome was susceptibility, based on cohort comparing COVID-19 positive and COVID-19 negative participants. RESULTS: There were a total of 290,455 patients from 12 studies in this meta-analysis. PPI use was associated with increased composite poor outcome (OR 1.85 [1.13, 3.03], p = 0.014; I2 90.26%). Meta-regression analysis indicate that the association does not vary by age (OR 0.97 [0.92, 1.02], p = 0.244), male (OR 1.05 [0.99, 1.11], p = 0.091), hypertension (OR 9.98 [0.95, 1.02], p = 0.317), diabetes (OR 0.99 [0.93, 1.05], p = 0.699), chronic kidney disease (OR 1.01 [0.93, 1.10], p = 0.756), non-steroidal anti-inflammatory drug use (OR 1.02 [0.96, 1.09], p = 0.499), and pre-admission/in-hospital PPI use (OR 0.77 [0.26, 2.31], p = 0.644). PPI use was not associated with the susceptibility to COVID-19 (OR 1.56 [0.48, 5.05], p = 0.46; I2 99.7%). CONCLUSION: This meta-analysis showed a potential association between PPI use and composite poor outcome, but not susceptibility. PROSPERO ID: CRD42020224286.


Subject(s)
COVID-19/complications , Proton Pump Inhibitors/adverse effects , Adult , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/physiopathology , Diabetes Mellitus , Disease Progression , Female , Humans , Hypertension , Male , Middle Aged , Renal Insufficiency, Chronic , Risk Factors , SARS-CoV-2 , Severity of Illness Index
17.
Arch Med Res ; 52(6): 656-659, 2021 08.
Article in English | MEDLINE | ID: covidwho-1157130

ABSTRACT

BACKGROUND: The ongoing Coronavirus Infectious Disease (COVID-19) pandemic is a global health crisis that has had a magnanimous worldwide impact on all aspects of people's lives. Several observational studies investigated the relationship between Proton Pump Inhibitors use and the risk of COVID-19 development and mortality. AIM OF THE STUDY: The aim of this meta-analysis is to investigate the association between current PPIs use and the development of COVID-19 as well as its mortality. METHODS: Pubmed, Google Scholar, ScienceDirect and medRxiv were searched until November 21, 2020 using the following keywords: proton pump inhibitors and COVID-19 as well as their related MESH terms. The studies considered in the meta-analysis were either cohort or case-control in design and adjusted for confounding factors. The quality of the studies included in this meta-analysis was assessed using the Newcastle-Ottawa Scale. In addition, a random-effects model was used to calculate the pooled Odds Ratio (ORs) and the corresponding confidence interval (95% CI). Heterogeneity was evaluated using The Cochran's Q heterogeneity test and I2 statistic. RESULTS: Six observational studies with 195,230 participants were included. In this meta-analysis, current use of PPIs increased risk of COVID-19 development (OR = 1.19; 95% CI: 0.62-2.28) and mortality (OR = 1.67; 95% CI: 1.41-1.97). CONCLUSIONS: Our meta-analysis indicates that current PPIs use significantly increased the risk of COVID-19 mortality, but it did not reach a significant threshold in regards to the risk of COVID-19 development.


Subject(s)
COVID-19 , Proton Pump Inhibitors , COVID-19/mortality , Humans , Observational Studies as Topic , Pandemics , Proton Pump Inhibitors/adverse effects , Risk Factors
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