Table 3.
Analysis of biomarkers at Week 20 across interventions (sensitivity analysis)
| Measures | Immediate vs. Gradual | Immediate vs. Control | Gradual vs. Control | |||
|---|---|---|---|---|---|---|
| Mean Difference/Ratio of Geometric Means1 (95% CI) |
P Value2 | Mean Difference/Ratio of Geometric Means1 (95% CI) |
P Value2 | Mean Difference/Ratio of Geometric Means1 (95% CI) |
P Value2 | |
| Linear Regression of Week 20 Biomarker, Adjusted For Baseline3 | ||||||
| 8-iso-PGF2α (pmol/mg creatinine) | 0.98 (0.92, 1.05) | 0.60 | 0.93 (0.85, 1.00) | 0.060 | 0.94 (0.87, 1.02) | 0.16 |
| hs-CRP (mg/L) | 0.99 (0.89, 1.10) | 0.83 | 1.13 (0.99, 1.28) | 0.062 | 1.14 (1.00, 1.29) | 0.046 |
| hs-CRP (mg/L), ≤10 values only5 | 0.99 (0.90, 1.09) | 0.79 | 1.12 (0.99, 1.26) | 0.064 | 1.13 (1.01, 1.27) | 0.034 |
| WBC (103/μL) | −0.16 (−0.38, 0.06) | 0.16 | −0.09 (−0.35, 0.17) | 0.50 | 0.07 (−0.20, 0.34) | 0.61 |
| WBC (103/μL), ≤14 values only5 | −0.10 (−0.32, 0.12) | 0.38 | −0.13 (−0.40, 0.14) | 0.36 | −0.03 (−0.27, 0.22) | 0.83 |
| PGEM (pmol/mg creatinine) | 1.05 (0.94, 1.18) | 0.39 | 1.02 (0.87, 1.18) | 0.85 | 0.96 (0.84, 1.11) | 0.61 |
| Red cell count (106/μL) | 0.00 (−0.04, 0.04) | 0.92 | 0.01 (−0.03, 0.06) | 0.52 | 0.01 (−0.03, 0.06) | 0.56 |
| Hemoglobin (g/dL) | 0.00 (−0.12, 0.12) | 0.97 | −0.06 (−0.19, 0.07) | 0.37 | −0.06 (−0.19, 0.08) | 0.39 |
| Hematocrit (%) | 0.01 (−0.34, 0.37) | 0.94 | −0.19 (−0.60, 0.21) | 0.35 | −0.21 (−0.60, 0.19) | 0.30 |
| MCV (fL) | −0.04 (−0.38, 0.31) | 0.83 | −0.68 (−1.08, −0.28) | <0.001 | −0.64 (−1.03, −0.25) | 0.001 |
| MCH (pg) | −0.03 (−0.16, 0.10) | 0.68 | −0.23 (−0.38, −0.08) | 0.003 | −0.20 (−0.35, −0.05) | 0.008 |
| MCHC (g/dL) | 0.03 (−0.08, 0.14) | 0.55 | 0.02 (−0.10, 0.15) | 0.72 | −0.01 (−0.13, 0.11) | 0.86 |
| RDW (%) | −0.15 (−0.28, −0.03) | 0.018 | −0.21 (−0.34, −0.07) | 0.003 | −0.05 (−0.19, 0.09) | 0.46 |
| Platelet count (103/μL) | −2.56 (−8.35, 3.24) | 0.38 | 2.64 (−4.00, 9.29) | 0.43 | 5.20 (−1.07, 11.47) | 0.10 |
| MPV (fL) | 0.03 (−0.11, 0.18) | 0.64 | −0.01 (−0.14, 0.12) | 0.88 | −0.04 (−0.19, 0.10) | 0.54 |
| Linear Regression of Week 20 Biomarker, Adjusted For Baseline and Other Covariates4 | ||||||
| 8-iso-PGF2α (pmol/mg creatinine) | 0.98 (0.91, 1.04) | 0.47 | 0.92 (0.85, 1.00) | 0.051 | 0.95 (0.87, 1.03) | 0.19 |
| hs-CRP (mg/L) | 0.99 (0.89, 1.10) | 0.84 | 1.13 (1.00, 1.28) | 0.053 | 1.14 (1.01, 1.30) | 0.041 |
| hs-CRP(mg/L), ≤10 values only5 | 0.99 (0.90, 1.09) | 0.86 | 1.12 (1.00, 1.26) | 0.059 | 1.13 (1.01, 1.27) | 0.038 |
| WBC (103/μL) | −0.18 (−0.40, 0.05) | 0.13 | −0.11 (−0.37, 0.16) | 0.43 | 0.07 (−0.20, 0.34) | 0.62 |
| WBC (103/μL), ≤14 values only5 | −0.11 (−0.34, 0.11) | 0.32 | −0.14 (−0.40, 0.13) | 0.31 | −0.03 (−0.27, 0.22) | 0.84 |
| PGEM (pmol/mg creatinine) | 1.05 (0.93, 1.18) | 0.41 | 1.01 (0.87, 1.18) | 0.87 | 0.96 (0.84, 1.11) | 0.60 |
| Red cell count (106/μL) | 0.00 (−0.04, 0.04) | 0.90 | 0.01 (−0.03, 0.06) | 0.56 | 0.01 (−0.03, 0.05) | 0.63 |
| Hemoglobin (g/dL) | 0.00 (−0.12, 0.12) | 0.97 | −0.07 (−0.20, 0.06) | 0.31 | −0.07 (−0.20, 0.07) | 0.34 |
| Hematocrit (%) | 0.02 (−0.34, 0.38) | 0.92 | −0.21 (−0.61, 0.20) | 0.32 | −0.23 (−0.62, 0.17) | 0.26 |
| MCV (fL) | −0.08 (−0.39, 0.30) | 0.80 | −0.68 (−1.09, −0.28) | <0.001 | −0.64 (−1.03, −0.25) | 0.001 |
| MCH (pg) | −0.03 (−0.16, 0.10) | 0.70 | −0.23 (−0.38, −0.08) | 0.003 | −0.20 (−0.35, −0.06) | 0.007 |
| MCHC (g/dL) | 0.03 (−0.07, 0.14) | 0.53 | 0.01 (−0.11, 0.14) | 0.85 | −0.02 (−0.14, 0.10) | 0.71 |
| RDW (%) | −0.15 (−0.28, −0.03) | 0.018 | −0.21 (−0.34, −0.07) | 0.003 | −0.05 (−0.19, 0.09) | 0.47 |
| Platelet count (103/μL) | −2.12 (−7.98, 3.74) | 0.47 | 2.59 (−4.03, 9.22) | 0.44 | 4.71 (−1.66, 11.09) | 0.15 |
| MPV (fL) | 0.03 (−0.12, 0.18) | 0.68 | −0.01 (−0.13, 0.12) | 0.94 | −0.04 (−0.18, 0.11) | 0.63 |
Mean difference for WBC, red cell count, hemoglobin, hematocrit, MCV, MCH, MCHC, RDW, platelet count, and MPV; ratio of geometric means for 8-iso-PGF2α, PGEM, and hs-CRP.
P < 0.00057 were considered statistically significant for secondary endpoints (8-iso-PGF2α, hs-CRP, and WBC); hs-CRP (≤ 10 values only) and WBC (≤ 14 values only) were analyzed as a sensitivity analysis for their respective non-restricted counterparts, hence the same P-value cutoff points were applied; P < 0.0167 were considered statistically significant for all the other biomarkers which are exploratory endpoints.
Linear regression of the Week 20 biomarker adjusted for the corresponding baseline measure; log-transformation was used for 8-iso-PGF2α, PGEM, and hs-CRP.
Linear regression of the Week 20 biomarker adjusted for the corresponding baseline measure, study site, together with any baseline variables which were different between treatment arms at P<0.20 (employment, Fagerström Test for Nicotine Dependence, and serum nicotine metabolic ratio); log-transformation was used for 8-iso-PGF2α, PGEM, and hs-CRP.
Analysis conducted excluding out-of-range values.
Abbreviation: 8isoPGF2α (pmol/mg), (Z)-7-[1R,2R,3R,5S]-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid) or 8-iso-prostaglandin F2α; hs-CRP, high sensitivity C Reactive Protein; WBC (103/μL), white cell count; PGEM (pmol/ml), Prostaglandin E Metabolite; MCV (fL), mean corpuscular volume (measure of size of red blood cells); MCH (pg), mean corpuscular hemoglobin (quantity of hemoglobin in red blood cell), MCHC (g/dL), mean corpuscular hemoglobin concentration (concentration of hemoglobin in red blood cells); RDW (%), red blood cell distribution, (variation in size and volume of red blood cells); MPV (fL), mean platelet volume (size of platelet)