Pairwise analysis - ncbi.nlm.nih.gov

FINAL Use of phosphate binders

Chronic kidney disease: evidence reviews for the use of phosphate binders FINAL (August 2021)

642

Pairwise analysis

Adults with stage 4 or 5 CKD who are not on dialysis Calcium acetate vs Placebo

Quality assessment No of patients Effect

Quality

No of studies

Design Risk of

bias Inconsistency Indirectness Imprecision

Other considerations

Calcium acetate

Placebo Relative (95% CI)

Absolute

Serum Phosphate (mmol/L) at 3 months (Better indicated by lower values) [MID +/- 0.22]

11 randomised trials

serious2 no serious inconsistency

no serious indirectness

serious3 none 37 41 - MD 0.23 lower (0.42 to 0.04

lower)

LOW

Proportion achieving phosphate control




serious3 none 22/37 (59.5%)

36.6% RR 1.63 (1 to 2.63)

23 more per 100 (from 0 more to 60

more)

LOW

Serum Calcium (mmol/L) at 3 months (Better indicated by lower values) [MID +/- 0.10]




serious3 none 37 41 - MD 0.17 higher (0.08 to 0.26

higher)

LOW

Risk of hypercalcaemia



643




very serious4

none 5/37 (13.5%)

0% RR 12.16 (0.7 to

212.64)

- VERY LOW

All-cause mortality




Serious5 none 1/46 (2.2%)

4.7% RR 0.46 (0.05 to 4.32)

3 fewer per 100 (from 4 fewer to

16 more)

VERY LOW

Discontinuation due to adverse events




very serious4

none 2/46 (4.3%)

6.3% RR 0.7 (0.13 to 3.64)


17 more)

VERY LOW

Adherence (Better indicated by higher values) [MID +/- 7]




serious3 none 37 41 - MD 0.7 lower (7.16 lower to 5.76 higher)

LOW

1 Qunibi 2011 2 Study at moderate or high risk of bias 3 95% confidence interval crosses one end of a defined MID interval 4 95% confidence interval crosses both ends of a defined MID interval 5 95% confidence interval crosses line of no effect Calcium carbonate vs Lanthanum carbonate


Quality

No of studies

Design Risk of



Calcium carbonate

Lanthanum carbonate

Relative (95% CI)

Absolute



644



very serious2

no serious inconsistency



VERY LOW



very serious2



very serious4

none 16 16 - MD 0.05 lower (0.15 lower to 0.05 higher)

VERY LOW

1 Soriano 2013 2 Study at high risk of bias 3 95% confidence interval crosses one end of a defined MID interval 4 95% confidence interval crosses both ends of a defined MID interval Lanthanum carbonate vs Placebo


Quality

No of studies

Design Risk of



Lanthanum carbonate


Absolute

Serum Phosphate (mmol/L) - Less than 3 months (Better indicated by lower values) [MID +/- 0.15]


very serious2

very serious3 no serious indirectness


lower)

VERY LOW



very serious2

serious5 no serious indirectness

no serious imprecision

none 57/142 (40.1%)

18.7% RR 2.37 (1.44 to

3.9)

26 more per 100 (from 8 more to

54 more)

VERY LOW



645

Serum Calcium (mmol/L) - Less than 3 months (Better indicated by lower values) [MID +/- 0.05]


very serious7




higher)

VERY LOW

Adverse events: constipation




serious none 14/86 (16.3%)

5.5% RR 2.98 (0.9 to 9.91)

11 more per 100 (from 1 fewer to

49 more)

LOW

Adverse events: nausea and/or vomiting


very serious2

serious5 no serious indirectness

very serious10 none 18/164 (11%)

6.7% RR 1.74 (0.72 to

4.2)


21 more)

VERY LOW



very serious2




11.2% RR 0.44 (0.18 to 1.04)


0 more)

VERY LOW

1 Sprague 2009; Takahara 2014 2 >33.3% of weighted data from studies at high risk of bias 3 i-squared >66.7% 4 95% confidence interval crosses one end of a defined MID interval 5 i-squared >33.3% 6 Sprague 2009 7 Study at high risk of bias 8 Takahara 2014 9 Study at moderate risk of bias 10 95% confidence interval crosses both ends of a defined MID interval Sevelamer hydrochloride vs Calcium acetate



646


Quality No of

studies Design

Risk of bias

Inconsistency Indirectness Imprecision Other

considerations Sevelamer

hydrochloride Calcium acetate

Relative (95% CI)

Absolute

Serum Phosphate (mmol/L) - Less than 3 months (Better indicated by lower values) [MID +/- 0.11]


very serious2



very serious3


VERY LOW

Serum Calcium (mmol/L) - Less than 3 months (Better indicated by lower values) [MID +/- 0.03]

1 randomised trials

very serious2




lower)

VERY LOW

1 Yilmaz 2012 2 Study at high risk of bias 3 95% confidence interval crosses both ends of a defined MID interval 4 95% confidence interval crosses one end of a defined MID interval Ferric citrate vs Placebo


Quality

No of studies

Design Risk of



Ferric citrate


Absolute



very serious2




none 57 29 - MD 0.41 lower (0.56 to 0.26

lower)

LOW



647



very serious2




none 37/57 (64.9%)

6.9% RR 9.41 (2.44 to 36.34)

58 more per 100 (from 10 more to

100 more)

LOW



very serious2




higher)

VERY LOW

All-cause mortality


very serious2




0% RR 1.52 (0.06 to 36.34)

- VERY LOW

Adverse events: constipation


very serious2



very serious5 none 7/57 (12.3%)

6.9% RR 1.78 (0.39 to 8.03)


49 more)

VERY LOW

Adverse events: diarrhoea


very serious2




6.9% RR 2.04 (0.46 to 8.97)


55 more)

VERY LOW

Adverse events: nausea and/or vomiting


very serious2




6.9% RR 0.25 (0.02 to 2.69)


12 more)

VERY LOW




648


very serious2




3.3% RR 3 (0.38 to 23.8)


75 more)

VERY LOW

1 Yokoyama 2014a 2 Study at high risk of bias 3 95% confidence interval crosses one end of a defined MID interval 4 95% confidence interval crosses line of no effect 5 95% confidence interval crosses both ends of a defined MID interval Calcium carbonate + low phosphate diet vs Low phosphate diet


Quality

No of studies

Design Risk of



Calcium carbonate +

low phosphate diet

Low phosphate

diet

Relative (95% CI)

Absolute



very serious2




higher)

VERY LOW



very serious2



very serious4


VERY LOW

Cardiovascular mortality


very serious2



Serious5 none 0/30 (0%)

3.3% RR 0.17 (0.01 to 3.99)

3 fewer per 100 (from 3 fewer to 10 more)

VERY LOW



649

Coronary artery calcification (Better indicated by lower values) ) [MID +/- 182.5]


very serious2



very serious4

none 29 14 - MD 74 higher (318.71 lower

to 466.71 higher)

VERY LOW

1 Russo 2007 2 Study at high risk of bias 3 95% confidence interval crosses one end of a defined MID interval 4 95% confidence interval crosses both ends of a defined MID interval 5 95% confidence interval crosses line of no effect Sevelamer hydrochloride + low phosphate diet vs Low phosphate diet


Quality

No of studies

Design Risk of



Sevelamer hydrochloride + low phosphate

diet

Low phosphate

diet

Relative (95% CI)

Absolute



very serious2



serious3 none 27 14 - MD 0.29 higher (0.10 to 0.48 higher)

VERY LOW



very serious2




VERY LOW

Cardiovascular mortality



650


very serious2



serious4 none 0/30 (0%)

3.3% RR 0.17 (0.01 to 3.99)

3 fewer per 100 (from 3 fewer to 10

more)

VERY LOW

Coronary artery calcification (Better indicated by lower values) [MID +/- 471.2]


very serious2



serious3 none 27 29 - MD 94 lower (646.86 lower

to 458.86 higher)

VERY LOW

1 Russo 2007 2 Study at high risk of bias 3 95% confidence interval crosses one end of a defined MID interval 4 95% confidence interval crosses line of no effect

Children and young people with stage 5 CKD who are on dialysis

Calcium carbonate vs Sevelamer hydrochloride


Quality

No of studies

Design Risk of



Calcium carbonate

Sevelamer hydrochloride

Relative (95% CI)

Absolute

Serum Phosphate (mmol/L) - 3 months (Better indicated by lower values) [MID +/- 0.25]


very serious2



serious3 none 14 15 - MD 0.11 higher (0.2 lower to 0.42 higher)

VERY LOW

Serum Phosphate (mmol/L) - 6 months (Better indicated by lower values) [MID +/- 0.09]



651


very serious2




VERY LOW

Serum Calcium (mmol/L) - 3 months (Better indicated by lower values) [MID +/- 0.07]


very serious2




none 14 15 - MD 0.23 higher (0.12 to 0.34

higher)

LOW

Serum Calcium (mmol/L) - 6 months (Better indicated by lower values) [MID +/- 0.07]


very serious2




VERY LOW

1 Salusky 2005 2 Study at high risk of bias 3 95% confidence interval crosses one end of a defined MID interval

Sucroferric oxyhydroxide vs Calcium acetate


Quality

No of studies

Design Risk of



Sucroferric oxyhydroxide

Calcium acetate

Relative (95% CI)

Absolute

Serum Phosphate (mmol/L) - 24 weeks (Better indicated by lower values) [MID +/-0.27]

1 randomised trials1

no serious risk of bias



serious2 none 36 6 - MD 0.49 higher (0.09 lower to 1.07

higher)

MODERATE

Serum Calcium (mmol/L) - 24 weeks (Better indicated by lower values) [MID +/-0.11]



652





very serious3 none 41 8 - MD 0.01 higher (0.15 lower to 0.17

higher)

LOW

Proportion with hypercalcaemia (Participants who developed ≥1 episode of sustained hypercalcemia [elevated serum calcium confirmed by repeat sample 1 week later] after start of treatment)






none 4/66 (6.1%)

4/19 (21.1%)

RR 0.28 (0.08 to 1.04)

15 fewer per 100 (from 19

fewer to 1 more)

MODERATE

Adverse events: Constipation






1/19 (5.3%)

RR 0.86 (0.1 to 7.83)


more)

LOW

Adverse events: Diarrhoea






0/19 (0%)

RR 6.87 (0.42 to 111.45)

- LOW

Adverse events: Nausea or vomiting






3/19 (15.8%)

RR 0.77 (0.23 to 2.61)


more)

LOW




653






6/19 (31.6%)

RR 0.58 (0.25 to 1.33)


more)

LOW

Adherence – mean percentage of adherence (Better indicated by higher values) [MID +/-19.0]





serious2 none 66 19 - MD 17.30 higher (0.68

lower to 35.28 higher)

MODERATE

1 Greenbaum 2020 2 95% confidence interval crosses one end of a defined MID interval 3 95% confidence interval crosses both ends of a defined MID interval

Pairwise analysis - ncbi.nlm.nih.gov

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