Naldemedine compared to placebo for opioid‐induced bowel dysfunction in cancer and people receiving palliative care

Patient or population: people with cancer and people receiving palliative care with opioid‐induced bowel dysfunction

Settings: cancer care

Intervention: naldemedine

Comparison: placebo

Laxation response within 24 hours of dose

—

—

—

Not reported

Laxation response between day 1 and day 14^a

RR 1.93 (1.36 to 2.74)

NNTB 2.88 (2.04 to 4.92)

225 (1 study)

⊕⊕⊕⊝

Moderate^b

—

Effect on analgesia: opioid withdrawal^c

0.1 mg: MD ‐0.13 (‐0.57 to 0.31); 0.2 mg: MD ‐0.40 (‐0.87 to 0.07); 0.4 mg: MD ‐0.02 (‐0.45 to 0.41)

225 (1 study)

⊕⊕⊕⊝

Moderate^b

—

Effect on analgesia: pain intensity

—

—

—

Not reported

Serious adverse events^a

5 SAEs occurred, all in naldemedine group.

225 (1 study)

⊕⊕⊝⊝
Low^b,d

—

Adverse events^a

RR 1.36 (1.04 to 1.79)

225 (1 study)

⊕⊕⊕⊝

Moderate^b

—

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; MD: mean difference; NNTB: number needed to treat for an additional beneficial outcome; RR: risk ratio; SAE: serious adverse events.

GRADE Working Group grades of evidence
High quality: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different.
Low quality: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low quality: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Lower‐dose naldemedine compared to higher‐dose naldemedine for opioid‐induced bowel dysfunction in cancer and people receiving palliative care

Patient or population: people with cancer and people receiving palliative care with opioid‐induced bowel dysfunction

Setting: cancer care

Intervention: lower dose naldemedine 0.1 mg daily

Comparison: higher dose naldemedine 0.2 mg or 0.4 mg daily

Laxation response within 24 hours of dose

—

—

—

Not reported

Laxation response between day 1 and day 14^a

0.1 mg vs 0.2 mg: RR 0.73 (0.55 to 0.95)

0.1 mg vs 0.4 mg: RR 0.69 (0.53 to 0.89)

226 (1 study)

0.1 mg vs 0.2 mg: n = 113

0.1 mg vs 0.4 mg: n = 111

⊕⊕⊕⊝

Moderate^b

—

Effect on analgesia: opioid withdrawal

—

—

—

Not reported

Effect on analgesia: pain intensity

—

—

—

Not reported

Serious adverse events

—

—

—

Not reported

Adverse events

—

—

—

Not reported

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different.
Low quality: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low quality: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Naloxone compared with placebo for cancer and people receiving palliative care with opioid‐induced bowel dysfunction

Patient or population: people with cancer and people receiving palliative care with opioid‐induced bowel dysfunction

Settings: cancer care

Intervention: naloxone

Comparison: placebo

Laxation response within 24 hours of a dose

—

—

—

Not reported

Laxation response between day 1 and day 14

—

—

—

Not reported

Effect on analgesia: opioid withdrawal

—

—

—

Not reported

Effect on analgesia: pain intensity^a

No statistical difference in pain experienced when taking placebo or naloxone. Full data, including pre‐cross‐over results, were not provided.

17 (1 study)

⊕⊝⊝⊝
Very low^b

—

Serious adverse events

—

—

—

Not reported

Adverse events

—

—

—

Not reported

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

GRADE Working Group grades of evidence
High quality: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different.
Low quality: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low quality: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Oxycodone/naloxone prolonged release tablets compared with oxycodone prolonged‐released tablets for opioid‐induced bowel dysfunction

Patient or population: people with cancer and people receiving palliative care with opioid‐induced bowel dysfunction

Settings: cancer care

Intervention: oxycodone/naloxone prolonged‐release tablets

Comparison: oxycodone prolonged‐released tablets

Laxation response within 24 hours of dose

—

—

—

Not reported

Laxation response between day 1 and day 14

—

—

—

Not reported

Effect on analgesia: opioid withdrawal^c

Intervention group: mean 6.64 (SD 5.97) comparison group: mean 7.29 (SD 4.59) at 7 days

184 (1 study)

⊕⊕⊕⊝

Moderate^b

—

Effect on analgesia: pain intensity^a

Intervention group: mean 3.50 (SD 1.88) and comparison group: mean 3.52 (SD 1.80) at 4 weeks

184 (1 study)

⊕⊕⊕⊝

Moderate^b

Another study, Dupoiron 2017 also found outcome to be similar between trial arms, but did not provide any data.

Serious adverse events

RR 2.00 (95% CI 0.62 to 6.41)

184 (1 study)

⊕⊕⊝⊝

Low^b,d

—

Adverse events

RR 1.08 (95% CI 0.94 to 1.24)

234 (2 studies)

⊕⊕⊕⊝

Moderate^b

—

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; RR: risk ratio; SD: standard deviation.

GRADE Working Group grades of evidence
High quality: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different.
Low quality: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low quality: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

Methylnaltrexone compared to placebo for opioid‐induced bowel dysfunction in cancer and people receiving palliative care

Patient or population: people with cancer and people receiving palliative care with opioid‐induced bowel dysfunction

Setting: palliative care

Intervention: methylnaltrexone

Comparison: placebo

Laxation response within 24 hours of dose^a

RR 2.77 (1.91 to 4.04)

287
(2 studies)

⊕⊕⊕⊝

Moderate^b

—

Laxation response between day 1 and day 14 (specifically within 4 hours after 4 or more of the 7 doses)^a

RR 9.98 (4.96 to 20.09)

305
(2 studies)

⊕⊕⊕⊝

Moderate

^b,c

—

Effect on analgesia: opioid withdrawal^d

236

(2 studies)

⊕⊕⊕⊝

Moderate^b

‐

Effect on analgesia: pain intensity^e

287

(2 studies)

⊕⊕⊝⊝

Low^b,f

Another study, Bull 2015, found similar pain intensity experienced in trial arms, full data not provided.

Serious adverse events

RR 0.59 (0.38 to 0.93)

364
(2 studies)

⊕⊕⊕⊝

Moderate^b

—

Adverse events

RR 1.17

(CI 0.94 to 1.45)

518
(3 studies)

⊕⊕⊝⊝

Low^b,g

Heterogeneity was substantial (74%). It was explained in sensitivity analysis by omitting the trial at a high risk of bias because of small sizes. The effect estimate was reduced. The direction of effect not changed.

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; MD: mean difference; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Lower dose methylnaltrexone compared to higher dose for opioid‐induced bowel dysfunction in cancer and people receiving palliative care

Patient or population: people with cancer and people receiving palliative care with opioid‐induced bowel dysfunction

Setting: palliative care

Intervention 1: lower‐dose methylnaltrexone (study 1: 3 doses, 1 week, 1 mg; study 2: 1 dose, 0.15 mg/kg)

Intervention 2: higher‐dose methylnaltrexone (study 1: 3 doses, 1 week, 5‐12.5 mg; study 2: 1 dose, 0.30 mg/kg)

Laxation response within 24 hours of first dose^a

Study 1: RR 0.82 (0.41 to 1.66)

Study 2: RR 1.07 (0.81 to 1.42)

135 (2 studies)

Study 1: n = 33

Study 2: n = 102

⊕⊕⊝⊝

Low^b

Unable to combine study data as methylnaltrexone low and higher doses differed per trial

Laxation response^a

At 3 days: RR 0.47 (0.18 to 1.25)

33 participants (1 study)

⊕⊕⊝⊝

Low^b

Unable to combine study data as methylnaltrexone low and higher doses differed per trial

At 3 days: RR 0.21 (0.03 to 1.31)

Effect on analgesia: opioid withdrawal^c

MD ‐0.04 (‐0.73 to 0.65)

102 participants

(1 study)

⊕⊕⊝⊝

Low^b

Another study,Portenoy 2008, also found outcome to be similar between trial arms, but did not provide any data

Effect on analgesia: pain intensity^d

MD ‐0.51 (‐1.49 to 0.47)

102 participants

(1 study)

⊕⊕⊝⊝

Low^b

Another study, Portenoy 2008, also found outcome to be similar between trial arms, but did not provide any data

Serious adverse event

—

—

Not reported

Adverse event

Study 1: RR 1.00 (1.00 to 1.00)

Study 2: RR 0.90 (0.73 to 1.13)

135 (2 studies)

Study 1: n = 33

Study 2: n = 102

⊕⊕⊝⊝

Low^b

Unable to combine study data as methylnaltrexone low and higher doses differed per trial

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; MD: mean difference; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different.
Low quality: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low quality: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.