Simplified monitoring for hepatitis C virus treatment with glecaprevir plus pibrentasvir, a randomised non-inferiority trial.

BACKGROUND & AIMS: Direct-acting antiviral (DAA) therapy for HCV has high efficacy and limited toxicity. We hypothesised that the efficacy of glecaprevir-pibrentasvir for chronic HCV with a simplified treatment monitoring schedule would be non-inferior to a standard treatment monitoring schedule. METHODS: In this open-label multicentre phase IIIb trial, treatment-naïve adults with chronic HCV without cirrhosis were randomly assigned (2:1) to receive glecaprevir-pibrentasvir 300 mg-120 mg daily for 8 weeks administered with a simplified or standard monitoring strategy. Clinic visits occurred at baseline and post-treatment week 12 in the simplified arm, and at baseline, week 4, week 8, and post-treatment week 12 in the standard arm. Study nurse phone contact occurred at week 4 and week 8 in both arms. Participants requiring adherence support were not eligible, including those reporting recent injecting drug use. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12), with a non-inferiority margin of 6%. RESULTS: Overall, 380 participants (60% male, 47% genotype 1, 32% genotype 3) with chronic HCV were randomised and treated with glecaprevir-pibrentasvir in the simplified (n = 253) and standard (n = 127) arms. In the intention-to-treat population, SVR12 was 92% (95% CI 89%-95%) in the simplified and 95% (95% CI 92%-99%) in the standard arm (difference between arms -3.2%; 95% CI -8.2% to 1.8%) and did not reach non-inferiority. In the per-protocol population, SVR12 was 97% (95% CI 96%-99%) in the simplified and 98% (95% CI 96%-100%) in the standard arm. No treatment-related serious adverse events were reported. CONCLUSIONS: In patients with chronic HCV infection without cirrhosis, treatment with glecaprevir-pibrentasvir was safe and effective. In comparison to standard monitoring, a simplified monitoring schedule did not achieve non-inferiority. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03117569. LAY SUMMARY: Direct-acting antiviral (DAA) therapy for hepatitis C is highly effective and well tolerated. The SMART-C randomised trial evaluated an 8-week regimen of glecaprevir-pibrentasvir for hepatitis C treatment, using a simplified monitoring schedule that included no pathology tests or clinic visits during treatment. This simplified strategy produced a high cure rate (92%), but this was not equivalent to the standard monitoring schedule cure rate (95%).

Visual Performance of Daily-disposable Multifocal Soft Contact Lenses: A Randomized, Double-blind Clinical Trial.

SIGNIFICANCE: The present study highlights the differences between modern daily-disposable multifocal soft contact lenses to assist eye care practitioners in fitting presbyopic contact lens wearers. PURPOSE: The purpose of this study was to compare visual performance of three daily-disposable multifocal contact lenses. METHODS: Presbyopes (n = 72) wore 1-Day Acuvue Moist Multifocal, BioTrue ONEday for Presbyopia, and Dailies AquaComfort Plus Multifocal for 1 week in a prospective, randomized, double-blind, crossover clinical trial. After 1 week, high- and low-contrast visual acuities (HCVA, LCVA) were measured between 6 m and 40 cm and stereopsis at 40 cm. Subjective performance was assessed with 1- to 10-point rating scales for clarity, ghosting, driving vision, vision stability, ease of focusing, overall vision satisfaction, and ocular comfort. Willingness to purchase was reported with categorical responses. Linear mixed models and χ tests were used for analysis, and level of significance was set at 5%. RESULTS: BioTrue provided better HCVA and LCVA at distance than did Acuvue Moist (P ≤ .03). Subjectively, Acuvue Moist was rated lowest for distance clarity, distance ghosting, and driving vision (P ≤ .05). Acuvue Moist provided better HCVA at 70 to 40 cm and LCVA at 1 m to 40 cm than did BioTrue (P ≤ .01) and better LCVA at 1 m to 50 cm than did AquaComfort Plus (P ≤ .02). AquaComfort Plus also provided better HCVA and LCVA at 50 and 40 cm than did BioTrue (P ≤ .03). Acuvue Moist provided better stereopsis than did BioTrue (P = .02). Subjectively, BioTrue was rated lowest for near clarity (P ≤ .007) and lower than Acuvue Moist for intermediate clarity and near ghosting (P ≤ .04). No other differences were found between lenses (P > .05). CONCLUSIONS: BioTrue had better distance performance compared with near, whereas Acuvue Moist performed conversely. AquaComfort Plus performed reasonably overall.

Effects of relative negative spherical aberration in single vision contact lens visual performance.

OBJECTIVE: The study aimed to compare the visual performance of contact lenses with and without negative spherical aberration (SA) over 5 days of wear. METHODS: At baseline, 32 myopic participants (aged 18-33 years) were fitted in a randomized order with two lenses (test lens with minimal or no SA and 1-Day Acuvue Moist designed with negative SA) for 5 days (minimum 6 hours wear/day). Participants returned for a follow-up visit. This consisted of on-axis SA measurements; high- and low-contrast visual acuities at 6 m; high-contrast acuities at 70 and 40 cm; low-illumination, low-contrast acuity at 6 m; stereopsis at 40 cm; horizontal phorias at 3 m and 33 cm; and ±2.00 D monocular accommodative facility at 33 cm. Participants also rated (1-10 scale) vision quality (clarity and lack of ghosting for distance, intermediate, near, driving vision and vision stability during day- and night-time), overall vision satisfaction, ocular comfort, and willingness to purchase (yes/no response). RESULTS: 1-Day Acuvue Moist induced significantly (p<0.05) more negative SA at distance (Δ=0.078 µm) and near (Δ=0.064 µm) compared to the test lens, for a 6 mm pupil. There were no significant differences (p>0.05) in acuity, binocular vision, and all subjective metrics except vision stability between lenses where the test lens was rated to provide more stable vision (p<0.05). CONCLUSION: Contrary to expectations, incorporating negative SA in single vision soft contact lenses did not improve visual performance in non-presbyopic adult myopes.

Comparison of Extended Depth-of-Focus Prototype Contact Lenses With the 1-Day ACUVUE MOIST MULTIFOCAL After One Week of Wear.

OBJECTIVES: To compare visual performance of extended depth-of-focus (EDOF) prototypes with a new, center-near, commercial, multifocal contact lens. METHODS: Presbyopic participants (n=57) wore 1-Day ACUVUE MOIST MULTIFOCAL (1DAMM) and an EDOF prototype for one week in a double-masked, prospective, cross-over, randomized clinical trial. Manufacturers' guide was used to select the first pair of lens to be fit based on subjective distance refraction and near addition. After one week, high- and low-contrast visual acuities were measured at distance (6 m), intermediate (70 cm) and near (50 and 40 cm), and stereopsis at 40 cm. Subjective performance was assessed on a 1 to 10 numeric rating scale for vision clarity and lack of ghosting at distance, intermediate and near, vision stability, haloes at night time, overall vision satisfaction, and ocular comfort. Linear mixed models were used for analysis and the level of significance was set at 5%. RESULTS: 1DAMM was not significantly different from EDOF for high- or low-contrast visual acuity at any distance, or for stereopsis. Subjectively, EDOF was significantly better than 1DAMM for vision clarity at intermediate (P=0.033) and near (P<0.001), overall lack of ghosting (P=0.012), vision stability (P=0.004), and overall vision satisfaction (P=0.005). For all other subjective variables, there were no differences between EDOF and 1DAMM (P>0.05). CONCLUSIONS: EDOF prototype lenses offer improvements over the newly marketed 1DAMM lenses for several subjective variables.

Extended depth of focus contact lenses vs. two commercial multifocals: Part 2. Visual performance after 1 week of lens wear.

PURPOSE: To compare the visual performance of prototype contact lenses designed via deliberate manipulation of higher-order spherical aberrations to extend-depth-of-focus with two commercial multifocals, after 1 week of lens wear. METHODS: In a prospective, participant-masked, cross-over, randomized, 1-week dispensing clinical-trial, 43 presbyopes [age: 42-63 years] each wore AIROPTIX Aqua multifocal (AOMF), ACUVUE OASYS for presbyopia (AOP) and extended-depth-of-focus prototypes (EDOF) appropriate to their add requirements. Measurements comprised high-contrast-visual-acuity (HCVA) at 6m, 70cm, 50cm and 40cm; low-contrast-visual-acuity (LCVA) and contrast-sensitivity (CS) at 6m and stereopsis at 40cm. A self-administered questionnaire on a numeric-rating-scale (1-10) assessed subjective visual performance comprising clarity-of-vision and lack-of-ghosting at various distances during day/night-viewing conditions and overall-vision-satisfaction. RESULTS: EDOF was significantly better than AOMF and AOP for HCVA averaged across distances (p≤0.038); significantly worse than AOMF for LCVA (p=0.021) and significantly worse than AOMF for CS in medium and high add-groups (p=0.006). None of these differences were clinically significant (≤2 letters). EDOF was significantly better than AOMF and AOP for mean stereoacuity (36 and 13 seconds-of-arc, respectively: p≤0.05). For clarity-of-vision, EDOF was significantly better than AOP at all distances and AOMF at intermediate and near (p≤0.028). For lack-of-ghosting averaged across distances, EDOF was significantly better than AOP (p<0.001) but not AOMF (p=0.186). EDOF was significantly better than AOMF and AOP for overall-vision-satisfaction (p≤0.024). CONCLUSIONS: EDOF provides better intermediate and near vision performance than either AOMF or AOP with no difference for distance vision after 1 week of lens wear.

Short-term comparison between extended depth-of-focus prototype contact lenses and a commercially-available center-near multifocal.

PURPOSE: To compare the visual performance of prototype contact lenses which extend depth-of-focus (EDOF) by deliberate manipulation of multiple higher-order spherical aberration terms and a commercially-available center-near lens (AIR OPTIX Aqua Multifocal, AOMF). METHODS: This was a prospective, cross-over, randomized, single-masked (participant), short-term clinical trial where 52 participants (age 45-70 years) were stratified as low, medium or high presbyopes and wore EDOF and AOMF on different days. Objective measures comprised high and low contrast visual acuity (HCVA/LCVA, logMAR), and contrast sensitivity (log units) at 6m; HCVA at 70cm, 50cm and 40cm and stereopsis (seconds of arc) at 40cm. HCVA at 70cm, 50cm and 40cm were measured as "comfortable acuity" rather than conventional resolution acuity. Subjective measures comprised clarity-of-vision and ghosting at distance, intermediate and near, overall vision satisfaction and ocular comfort (1-10 numeric rating scale) and lens purchase (yes/no response). Statistical analysis included repeated measures ANOVA, paired t-tests and McNemar's test. RESULTS: Significant differences between lens types were independent of strata (p≥0.119). EDOF was significantly better than AOMF for HCVA at 40cm (0.42±0.18 vs. 0.48±0.22, p=0.024), stereopsis (98±88 vs. 141±114, p<0.001), clarity-of-vision at intermediate (8.5±1.6 vs. 7.7±1.9, p=0.006) and near (7.3±2.5 vs. 6.2±2.5, p=0.005), lack-of-ghosting (p=0.012), overall vision satisfaction (7.5±1.7 vs. 6.4±2.2, p<0.001) and ocular comfort (9.0±1.0 vs. 8.3±1.7, p=0.002). Significantly more participants chose to only-purchase EDOF (33% vs. 6%, p=0.003).). There were no significant differences between lens types for any objective measure at 6m or clarity-of-vision at distance (p≥0.356). CONCLUSIONS: EDOF provides better intermediate and near vision performance in presbyopes than AOMF with no difference for distance vision during short-term wear.