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Fixed-dose combination therapy-based protocol compared with free pill combination protocol: Results of a cluster randomized trial.

ABSTRACT: Fixed-dose combination (FDC) therapy is recommended for hypertension management in Nigeria based on randomized trials at the individual level. This cluster-randomized trial evaluates effectiveness and safety of a treatment protocol that used two-drug FDC therapy as the second and third steps for hypertension control compared with a protocol that used free pill combinations. From January 2021 to June 2021, 60 primary healthcare centers in the Federal Capital Territory of Nigeria were randomized to a protocol using FDC therapy as second and third steps compared with a protocol that used the same medications in free pill combination therapy for these steps. Eligible patients were adults (≥18 years) with hypertension. The primary outcome was the odds of a patient being controlled at their last visit between baseline to 6-month follow-up in the FDC group compared to the free pill group. 4427 patients (mean [SD] age: 49.0 [12.4] years, 70.5% female) were registered with mean (SD) baseline systolic/diastolic blood pressure 155 (20.6)/96 (13.1) mm Hg. Baseline characteristics of groups were similar. After 6-months, hypertension control rate improved in the two treatment protocols, but there were no differences between the groups after adjustment (FDC = 53.9% versus free pill combination = 47.9%, cluster-adjusted p = .29). Adverse events were similarly low (<1%) in both groups. Both protocols improved hypertension control rates at 6-months in comparison to baseline, though no differences were observed between groups. Further work is needed to determine if upfront FDC therapy is more effective and efficient to improve hypertension control rates.

SUBMITTER: Sanuade OA

PROVIDER: S-EPMC9903187 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Fixed-dose combination therapy-based protocol compared with free pill combination protocol: Results of a cluster randomized trial.

Sanuade Olutobi A OA Ale Boni M BM Baldridge Abigail S AS Orji Ikechukwu A IA Shedul Gabriel L GL Ojo Tunde M TM Shedul Grace G Ugwuneji Eugenia N EN Egenti Nonye N Omitiran Kasarachi K Okoli Rosemary R Eze Helen H Nwankwo Ada A Hirschhorn Lisa R LR Chopra Aashima A Ye Jiancheng J Tripathi Priya P Banigbe Bolanle B Kandula Namratha R NR Huffman Mark D MD Ojji Dike B DB

Journal of clinical hypertension (Greenwich, Conn.) 20230120 2

Fixed-dose combination (FDC) therapy is recommended for hypertension management in Nigeria based on randomized trials at the individual level. This cluster-randomized trial evaluates effectiveness and safety of a treatment protocol that used two-drug FDC therapy as the second and third steps for hypertension control compared with a protocol that used free pill combinations. From January 2021 to June 2021, 60 primary healthcare centers in the Federal Capital Territory of Nigeria were randomized t ...[more]

PMID: 36660886

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Project description:Purpose: The aims of this study was to investigate the mutual pharmacokinetic interactions between steady-state atorvastatin and metformin and the effect of food on the fixed-dose combined (FDC) tablet of atorvastatin and metformin extended release (XR). Subjects and methods: Study 1, an open-labeled, fixed sequence, multiple-dose pharmacokinetic drug-drug interaction study, was divided into 2 parts. Atorvastatin (40 mg) or metformin (1,000 mg) XR tablets were administered once daily via mono- or co-therapy for 7 days. Plasma levels of atorvastatin and 2-OH-atorvastatin, were quantitatively determined for 36 h in part A (n=50) while metformin plasma concentration was measured up to 24 h in part B (n=16) after the last dosing. Study 2, a randomized, open-labeled, single-dose, two-treatment, two-period, two-sequence crossover study, involved 27 healthy subjects to investigate the impact of food intake on the pharmacokinetics of a combined atorvastatin/metformin XR 20/500 mg (CJ-30056 20/500 mg) tablet. Results: After multiple doses of mono- or co-therapy of atorvastatin (40 mg) and metformin (1,000 mg) XR, the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for the peak plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve during the dosing interval at steady state (AUCτ,ss) were 1.07 (0.94-1.22) and 1.05 (0.99-1.10) for atorvastatin, 1.06 (0.96-1.16) and 1.16 (1.10-1.21) for 2-OH-atorvastatin, and 1.00 (0.86-1.18) and 0.99 (0.87-1.13) for metformin, respectively. Food delayed time to reach maximum concentration (tmax), decreased atorvastatin Cmax by 32% with a GMR (90% CI) of 0.68 (0.59-0.78), and increased metformin AUCt by 56% with a GMR (90% CI) of 1.56 (1.43-1.69). Conclusion: No clinically relevant pharmacokinetic interaction was seen when atorvastatin was co-administered with metformin. Food appeared to change the absorption of atorvastatin and metformin from an FDC formulation. These alterations were in accordance with those described with the single reference drugs when ingested with food.

Project description:BackgroundThe addition of ezetimibe to statin therapy has been reported to result in increased efficacy for reduction of LDL-C levels and achievement of lipid targets, compared with monotherapy.ObjectiveThis study was designed to demonstrate the noninferiority of therapy with fixed-dose rosuvastatin plus ezetimibe formulations versus fixed dose simvastatin and ezetimibe formulations for reduction of LDL-C levels in Brazilian patients with hypercholesterolemia or mixed dyslipidemia.MethodsPhase III, multicenter, randomized, parallel, open-label, noninferiority study that included male and female participants (aged 21-80 years) with hypercholesterolemia or mixed dyslipidemia. After a 1-week screening period with washout of lipid-lowering medications when needed, patients were treated with simvastatin 20 mg/d for 5 weeks. Participants with LDL-C levels ≥100 mg/dL after the initial treatment were submitted to a 1-week washout period, and then randomized 1:1 to receive either combined rosuvastatin 10 mg + ezetimibe 10 mg (R/E) or simvastatin 20 mg + ezetimibe 10 mg (S/E) for 4 weeks and, if they still did not achieve the stipulated target, doses were readjusted to rosuvastatin 20 mg + ezetimibe 10 mg or simvastatin 40 mg + ezetimibe 10 mg, respectively, for 4 weeks.ResultsOne hundred twenty-nine participants were enrolled, including 66 in R/E and 63 in S/E. At the end of simvastatin 20 mg treatment period, mean LDL-C values were 124.79 mg/dL and 121.27 mg/dL for participants randomized to R/E and S/E arms, respectively. After 4 weeks of R/E 10 mg + 10 mg or S/E 20 mg + 10 mg combined treatments, adjusted mean LDL-C values were 74.21 mg/dL and 85.58 mg/dL, respectively (P = 0.0005), and after 9 weeks, with dose adjustment to R/E 20 mg + 10 mg in 6 patients and to S/E 40 mg +10 mg in 19 patients, LDL-C adjusted mean values were 75.29 mg/dL and 86.62 mg/dL, respectively (P = 0.0006). There was a statistically significant difference between the association R/E and S/E (P = 0.0013) in percentage change of LDL-C after 9 weeks of combined treatments. The adjusted mean difference was estimated at -10.32% (95% CI, -16.94% to -3.70%). The LDL-C <100 mg/dL target was achieved in a significantly greater proportion of participants at week 4 in the R/E compared with the S/E arm (84.8% vs 68.2%; P = .0257), and at week 9, the proportion was 81.2% versus 73.0%, respectively (P = 0.23). LDL-C <70 mg/dL was achieved at a significantly greater proportion in the R/E arm, both at week 4 (45.4% vs 15.9%; P = 0.003) and week 9 (40.9% vs 15.9%; P = 0.0017). A statistically significant difference at week 9 (P = 0.0106) was observed in fasting blood glucose in the R/E arm, but the overall incidence of adverse events was not significantly different between groups.ConclusionsRosuvastatin and ezetimibe fixed dose combination in both 10 mg/10 mg and 20 mg/10 mg doses, respectively, provided significantly lower levels of LDL-C compared with simvastatin and ezetimibe in doses of 20 mg/10 mg and 40 mg/10 mg, respectively. The fixed-dose combinations were both effective and well tolerated in this Brazilian study population. ClinicalTrials.gov identifier: NCT01420549. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Project description:PurposeTo compare the safety and efficacy of fixed-dose tafluprost/timolol combination (Taf/T-FDC) with those of fixed-dose latanoprost/timolol combination (Lat/T-FDC) by measuring the intraocular pressure (IOP)-lowering effect, ocular pharmacokinetics, and ocular surface toxicity.MethodsThe IOP-lowering effect of Taf/T-FDC and Lat/T-FDC in ocular normotensive monkeys was evaluated at 4 and 8 h after instillation in study A, at 12, 14, 16, and 18 h after instillation in study B, and at 24, 26, 28, and 30 h after instillation in study C. Drug penetration into the eye was evaluated by measuring the concentrations of timolol, tafluprost acid (active metabolic form of tafluprost), and latanoprost acid (active metabolic form of latanoprost) using liquid chromatography coupled with tandem mass spectrometry after single instillation of Taf/T-FDC or Lat/T-FDC to Sprague Dawley rats. Cytotoxicity following 1-30 min exposure of SV40-transformed human corneal epithelial cells to Taf/T-FDC or Lat/T-FDC was analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assays. Undiluted and 10-fold diluted solutions of each FDC were evaluated.ResultsThe IOP-lowering effect of Taf/T-FDC was almost equivalent to that of Lat/T-FDC at 4-8 h after instillation. The peak IOP reduction of Taf/T-FDC and Lat/T-FDC was observed at 8 h after instillation, and there is no difference between the two. The difference between them was observed at 24-30 h after instillation, and Taf/T-FDC demonstrated a significantly greater IOP-lowering effect than Lat/T-FDC at 24-30 h after instillation. The IOP-lowering effect of Taf/T-FDC was sustained up to 30 h after instillation, while that of Lat/T-FDC had almost disappeared at 28 h after instillation. Timolol concentrations in aqueous humor after Taf/T-FDC instillation were higher than those after Lat/T-FDC instillation (Cmax, 3870 ng/mL vs 1330 ng/mL; AUCinf, 3970 ng·h/mL vs 1250 ng·h/mL). The concentrations of tafluprost acid and latanoprost acid in aqueous humor after instillation of Taf/T-FDC and Lat/T-FDC, respectively, were similar to those after instillation of mono-preparations of tafluprost and latanoprost, respectively. The cytotoxic effect of Taf/T-FDC to the human corneal epithelial cells was significantly lower than that of Lat/T-FDC at all evaluated time points in both undiluted and 10-fold diluted FDCs.ConclusionTaf/T-FDC provides increased IOP-lowering effect duration and lower potential ocular surface toxicity than Lat/T-FDC.

Project description:BackgroundA significant proportion of cardiovascular disease (CVD) morbidity and mortality could be prevented via the population-based and cost-effective interventions. A fixed-dose combination treatment is known as the polypill for the primary and secondary prevention of CVD has come up in recent years.PurposeIn order to provide recommendations for future economic evaluations, this systematic review aimed to review and assess the quality of published evidence on the cost-effectiveness of polypill in primary and secondary prevention of CVD, to identify the key drivers that impact the cost-effectiveness.MethodsA systematic review of literature, following the PRISMA guidelines, was undertaken in the electronic databases. Two researchers identified the relevant studies according to inclusion and exclusion criteria. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to quality assessment of included studies. ICERs value adjusted to 2020 United States Dollar using consumer price index (CPI) and purchasing power parity (PPP). Finally, data were summarized via a narrative synthesis.ResultsIn total, 24 articles were identified based on the determined inclusion criteria. All studies met more than 50% of the CHEERS criteria. Adjusted incremental cost-effectiveness ratios varied from 24$ to 31000$(2020 US dollar) among the studies. The polypill resulted in the improved adherence and quality of life, at a price equal to or lower than multiple monotherapies. This price is typically below the commonly accepted thresholds or cost saving in both, primary and secondary prevention of CVD. The main identified cost-effectiveness drivers were the polypill price, adherence, age, CVD risk, and drug combination.ConclusionsThis systematic review found that the polypill seemed to be a cost-effective intervention in primary and secondary prevention of CVD. However, it is necessary to conduct more economic evaluation studies based on the long-term clinical trials with large populations. Also, studies should consider how the polypill interacts with other primary and secondary preventive strategies as a complementary health strategy.

Project description:BackgroundAsthma guidelines suggest that therapy can be reduced once asthma is controlled. Despite these recommendations, asthmatic patients are seldom stepped down in clinical practice, and questions remain about when and how to reduce asthma therapy. The purpose of the present study was to evaluate lung function and asthma control in patients who were stepped down from the highest recommended dose of inhaled corticosteroid/long acting β2 agonist combination therapy.MethodsThis was a prospective, randomised, controlled, two-arm parallel group study. Asthmatic patients who were fully controlled with a high daily dose (1000/100 μg) of fluticasone/salmeterol were randomly assigned to 6 months of open-label treatment with either 500/100 μg fluticasone/salmeterol Diskus daily or 400/24 μg extrafine beclomethasone/formoterol pMDI daily. The primary outcome was the change in morning peak expiratory flow (PEF) values between baseline and the end of treatment. The secondary outcomes included asthma control and exacerbation frequency.ResultsFour hundred twenty-two patients were included in the analysis. The PEF values remained above 95% of the predicted values throughout the study. The end-study morning PEF rates showed equivalence between the groups (difference between means, 2.49 L/min; 95% CI, -13.43 to 18.42). No changes from baseline were detected in PEF and forced expiratory volume in 1 second measured at the clinics, in the symptom scores or in the use of rescue medication. Asthma control was maintained in 95.2% of the patients at 6 months. No significant differences between the groups were detected in any other parameter, including exacerbation frequency and adverse events.ConclusionsStepping down patients whose asthma is controlled with the highest recommended dose of fluticasone/salmeterol to either 500/100 μg fluticasone/salmeterol daily or 400/24 μg extra-fine beclomethasone/formoterol daily provides comparable maintenance of lung function and asthma control.Trial registrationclinicaltrials.gov NCT00497237.

Project description:IntroductionReducing intraocular pressure (IOP), the only modifiable risk factor for open-angle glaucoma (OAG), is important for the preservation of vision and slowing of disease progression. Preservative-free tafluprost (0.0015%)/timolol (0.5%) fixed combination (PF Taf-T FC) is an approved combination therapy for OAG treatment. The VISIONARY study aimed to evaluate the effectiveness and tolerability of PF Taf-T FC in real-world clinical settings. Here, we present the results from the United Kingdom (UK) and Ireland.MethodsThis observational, multicentre, European, prospective study recorded data during routine clinic appointments on the use of PF Taf-T FC for the treatment of OAG and ocular hypertension (OHT) in patients whose disease was insufficiently controlled on a prostaglandin analogue (PGA) or beta blocker monotherapy or who did not tolerate these medications. Mean change in IOP, symptom severity, changes in clinical signs, and tolerability were investigated over 6 months.ResultsEighty-two patients were recruited in the UK and Ireland. After 6 months of PF Taf-T FC treatment, mean IOP was significantly reduced from 22.0 to 16.2 mmHg in the UK group and from 18.6 to 14.1 mmHg in the Ireland group. In the UK (65 patients), 49 adverse events (AEs) were reported, of which 3 were serious. No AEs were reported in the Ireland group (17 patients). Overall, 91.9% of UK physicians reported PF Taf-T FC treatment to be the same or better than prior medication for improving clinical signs; 90.0% of UK patients reported PF Taf-T FC treatment to have good or very good tolerability.ConclusionsTreatment with PF Taf-T FC resulted in significant reductions in mean IOP over 6 months. Patients and physicians reported that treatment was well tolerated. These data demonstrate real-world efficacy of PF Taf-T FC for the treatment of OAG and OHT in routine clinical practice in the UK and Ireland.Trial registrationEuropean Union electronic Register of Post-Authorisation Studies (EU PAS) register number, EUPAS22204.

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Fixed-dose combination therapy-based protocol compared with free pill combination protocol: Results of a cluster randomized trial.

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Fixed-dose combination therapy-based protocol compared with free pill combination protocol: Results of a cluster randomized trial.

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