Table 14

Intracavernosal Injection: Patients with Adverse Events.

PGE₁ versus no treatment. One trial, involving men who had undergone nerve-sparing radical retropubic prostatectomy, compared efficacy and harms of PGE1 to those of no treatment.²⁶⁵

Harms. In total, 6.7 percent and 13.3 percent of participants treated with PGE₁ reported prolonged erection and hematoma, respectively. No untreated participants reported these adverse event s.

Efficacy. In total, 66.7 percent of participants receiving PGE₁ had improved erections versus 20 percent of those who did not receive any treatment. The absolute risk difference (RD) between the two groups was 47 percent (95 percent CI: 13–80).

PGE₁ versus placebo. Six trials compared efficacy and/or harms of PGE1 versus placebo.^{266, 268, 274, 281, 282, 292}

Harms. Penile pain was reported in four trials and occurred numerically more commonly in participants treated with PGE₁. In one trial, penile pain was reported by 22.7 percent of the participants treated with PGE₁ ²⁷¹ and in another in 13.3 percent of the participants.²⁸² Neither study reported data on pain for the placebo groups. A third trial reported pain to have occurred in 35 percent of the participants who received PGE₁ versus 0 percent of the placebo-treated participants²⁶⁶ The fourth trial observed similar proportions of patients with pain between the treatment groups (PGE₁: 11.7 percent versus placebo: 10.9 percent).²⁷⁴ Prolonged erection or priapism was reported by 15 percent ²⁶⁶ and 2.5 percent ²⁷¹ of the PGE₁ -treated participants. In placebo-treated subjects, none of the participants had priapism in the first trial, and no priapism-related data were reported for the second trial. In a single trial, hematoma was reported for 1.5 percent of injections with PGE₁, with no data reported for the placebo group.²⁸²

Efficacy. In four crossover trials, between 28.9 and 66 percent of participants reported improved erections in the PGE₁ treatment groups. In two of these trials, placebo-treated participants did not experience improved erections ^{266, 268} The other two trials did not report any outcomes data for the placebo groups.^{281, 292}

In one parallel trial, none of the placebo-treated participants reported improved erections, as compared with 35 percent of the participants treated with PGE₁. The observed pattern conformed a dose-response trend (17 percent with 2.5μ g PGE₁, 27 percent with 5μ g, 45 percent with 10μ g, and 50 percent with 20μ g).²⁷¹

PGE₁ versus PGE₁ (comparison of timing of treatment initiation or dose delivery). One trial compared the harms related to fast versus slow PGE1 injection (i.e., 5-second injection versus 60-second injection).²⁷⁰ A second trial, involving men who had undergone non-nerve-sparing radical prostatectomy, compared the efficacy and harms of early versus late post-prostatectomy PGE1 treatment (i.e., 1–3 months post-operatively versus 4–12 months post-operatively).²⁵⁶

Harms. In the first trial, 54.5 percent of those receiving fast PGE₁ injections reported pain during injection versus 18.2 percent of those receiving slow injections.²⁷⁰ In the second trial, 8.3 percent of participants who received early PGE₁ treatment reported prolonged erections versus 0 percent of those who received late PGE₁ treatment.²⁵⁶

Efficacy. In total 72.2 percent of participants receiving early PGE₁ treatment reported improved erections versus 43.2 percent of those receiving late PGE₁ treatment.²⁵⁶

PGE₁ versus papaverine. Four trials compared the efficacy and/or harms of PGE1 versus papaverine, ^{287, 288, 291, 293} Only one trial of intracavernosal injection evaluated the outcome of sexual intercourse success.²⁹¹

Harms. In three trials that reported penile pain, two^{288, 291} showed statistically nonsignificant differences between PGE₁ andpapaverine (8.5 percent versus 4.7 percent, and 46 versus 44 percent, respectively). ^{288, 291} The third trial reported more frequent occurrence of pain in the papaverine participants (32.7 percent versus 11.5 percent, RD 21 percent, 95 percent CI: 6.0–37.0).²⁸⁷ All four trials reported the incidence of priapism. In one trial, this occurred in 10 percent of the participants treated with PGE₁ versus 6.7 percent of those treated with papaverine.²⁹³ In two trials no cases of priapism occurred in either treatment group. ^{287, 288} In the fourth trial, no priapism occurred among PGE₁-treated subjects versus 0.8 percent of the participants among papaverine-treated subjects.²⁹¹

Efficacy. In one trial²⁹¹, the proportions of PGE₁- and papaverine-treated patients achieving at least one successful intercourse attempt over 4 weeks of treatment were similar (31 percent versus 33 percent).

In four trials, from 26.4 to 80.8 percent of the PGE₁-treated participants reported improved erections, as compared with 10 to 63.5 percent of papaverine-treated subjects. The estimates of RR favouring PGE₁ over papaverine were statistically significant in three trials ^{288, 291, 293} and marginally significant in the fourth trial.²⁸⁷

PGE₁ plus papaverine versus phentolamine plus papaverine. One trial compared efficacy and harms of papaverine plus PGE1 versus papaverine plus phentolamine.²⁸⁹

Harms. In total, 16.3 percent of the papaverine plus PGE₁ participants reported pain versus 0 percent of the papaverine plusphentolamine participants. Approximately 8 percent of the participants in each treatment group reported prolonged erection.

Efficacy. In total, 77.6 percent of participants allocated to papaverine plus PGE₁ reported improved erections versus 57.1 percent of participants allocated to papaverine plus phentolamine.

PGE₁ versus papaverine plus phentolamine. One trial compared the efficacy and harms of PGE1 versus papaverine plus phentolamine.²⁶⁶

Harms. In total, 35 percent of PGE₁ participants reported pain versus 15 percent of papaverine plus phentolamine participants. There was no difference in prolonged erections between the two treatments (15.0 percent versus 18.3 percent; RD -3.0 percent, 95 percent CI: -17.0 to 10.0)

Efficacy. In total, 50 percent of participants treated with PGE₁ reported improved erections versus 56.7 percent of those treated withpapaverine plus phentolamine.

PGE₁ versus trimix. (see papaverine plus phentolamine plus PGE₁ versus PGE₁ below)

PGE₁ versus moxisylate. Two trials compared the efficacy and harms of PGE1 to moxisylate.^{262, 293} In both trials, PGE1 was shown to be more effective than moxisylate.

Harms. In the first study, compared with participants in the moxisylate group, those in the PGE₁ group experienced the following events more frequently: pain during injection (14.8 versus 25 percent), pain during erection (4.9 versus 23.5 percent), pain after erection (4.9 versus 19.1 percent), prolonged erection (1.6 versus 4.4 percent), and bleeding (4.9 versus 14.7 percent), whereas, the occurrence of dizziness/hypotension was numerically more common in moxisylate-treated participants (8.2 versus 1.5 percent). Not all differences were statistically significant. In the second study, prolonged erection appeared more common in the participants treated with PGE₁ (3.3 versus 10 percent)

Efficacy. In the first trial, 85.3 percent of the participants treated with PGE₁ reported improved erections versus 60.7 percent of the moxisylate-treated participants.²⁶² In the second trial, the rates of improved erection in PGE₁ and moxisylate groups were 40 percent and. 6.7 percent, respectively.²⁹³

PGE₁ versus sodium nitroprusside. One trial compared the efficacy and harms of PGE1 with three different doses of nitroprusside (100μ g, 300μ g, or 400μ g).²⁷⁸

Harms. In total, 6.7 percent of the participants in PGE₁ group reported pain during injection versus 0 percent of those in each of the nitroprusside group. About 4.0 percent of the participants treated with PGE₁ reported dizziness versus 10, 8 and 3 percent for each of the nitroprusside groups(100μ g, 300μ g, and 400μ g, respectively).

Efficacy. In total, 20 percent of the participants treated with PGE₁ reported full rigidity. Nitroprusside 100μ g was reported to be ineffective in producing erections. In the 300μ g and 400μ g nitroprusside groups, 15 percent and 14.3 percent of the participants, respectively had full rigidity.

PGE₁ versus linsidomine. Three trials compared the efficacy and harms of PGE1 to linsidomine.^{273, 279, 284}

Harms. In one trial, 17.5 percent of participants receiving PGE₁ reported penile pain. Similar data for the linsidomine-treated subjects was not provided. In the linsidomine group, moderate to severe headache was reported by 7.5 percent of the subjects.²⁸⁴In a second trial, 7.5 percent of PGE₁ participants reported pain during injection versus 2.5 percent of linsidomine subjects.²⁷³

Efficacy. Between 30 and 65 percent of the participants treated with PGE₁ had improved erections compared with 7.5–12.5 percent of those treated with linsidomine.

PGE₁ versus linsidomine plus urapidil. One trial compared the efficacy and harms of PGE1 to linsidomine plus urapidil.²⁷³

Efficacy. In total, 40 percent of participants randomly assigned to PGE₁ therapy reported improved erections versus 25 percent of those randomly assigned to linsidomine plus urapidil therapy.

Harms. In total, 7.5 percent of participants in each treatment group reported pain during injection, while 0 percent of those receiving PGE₁ and 12.5 percent of those receiving linsidomine plus urapidil reported severe hypotension.

PGE₁ versus PGE₁ plus lidocaine. One trial compared the efficacy and harms of PGE1 injections with or without lidocaine.

Harms. The proportions of participants reporting pain in PGE₁ plus lidocaine versus PGE₁ only groups were 45.4 percent and 86.4 percent, respectively.

Efficacy. In total 63.6 percent of the participants allocated to PGE₁ plus lidocaine reported improved erections versus 27.3 percent of those allocated to PGE₁ alone.

PGE₁ versus PGE₁ plus procaine. One trial compared the efficacy and harms of PGE1 injections with and without procaine (10mg or 20mg).²⁸⁰

Harms. Of participants allocated to PGE₁ plus procaine, 62.5 percent reported moderate to severe pain compared with 83.3 percent of those allocated to treatment with PGE₁ only. The occurrence of severe pain was reported by 16.6 percent versus 45.8 percent of the participants, respectively.

Efficacy. In total, 66.7 percent of those assigned to receive PGE₁ plus procaine reported improved erections versus 66.7 percent of those assigned to receive PGE₁ only.

PGE₁ versus PGE₁ plus sodium bicarbonate. One trial compared the harms of PGE1 injections with or without sodium bicarbonate.²⁶⁹

Harms. In total, 70 percent of participants assigned to the PGE₁ plus sodium bicarbonate group reported pain versus 80 percent of those assigned to the PGE₁ group. The incidence of pain in PGE₁ plus sodium bicarbonate group was reduced compared with PGE₁ alone group but the between-group difference was not statistically significant (70 percent versus 80 percent, RD -10 percent, 95 percent CI: -48.0–28.0).

Efficacy. The efficacy was not reported

PGE₁ plus sexual counseling plus sildenafil versus PGE₁ plus sildenafil. One trial compared the efficacy and harms of PGE1 plus sexual counseling plus adjunctive open label oral sildenafil versus PGE1 plus adjunctive open label sildenafil in men who had undergone non-nerve sparing radical retropubic prostatectomy or radical cystectomy.²⁹⁴

Harms. The frequency of adverse events was similar for PGE₁ plus counseling plus sildenafil versus PGE₁ plus sildenafil groups, including moderate pain (34.4 percent versus 42.8 percent), severe pain (13.7 percent versus 10.7 percent), prolonged erection (17.2 percent versus 17.8 percent), and hematomas (6.9 percent versus 10.7 percent). There were no withdrawals among the participants allocated to PGE₁ plus counseling plus sildenafil. In contrast, 29 percent of those treated with PGE₁ plus sildenafil withdrew (3 of 8 withdrawals were due to prolonged pain after injections).

Efficacy. Mean score on the IIEF “EF domain” after 18 months of treatment was significantly higher in men allocated to PGE₁ plus counseling plus sildenafil versus those allocated to PGE₁ plus sildenafil (26.5 versus 24.3, p < 0.05).

Papaverine versus placebo. None of the identified studies compared papaverine monotherapy to placebo. One trial reported the efficacy and harms of papaverine plus PGE1 versus PGE1 alone.²⁸⁹ Papaverine plus PGE1 was not shown to be more effective and it was associated with more frequent pain than PGE1 alone.

Harms. In total 34.2 percent of participants allocated to papaverine plus PGE₁ reported pain versus 18.4 percent of those allocated to PGE₁ alone. The incidence of prolonged erection was reported by 15 percent and 18.3 percent of the participants in each group, respectively.

Efficacy. In total, 73.7 percent of participants allocated to papaverine plus PGE₁ reported improved erections versus 60.5 percent of those allocated to PGE₁ alone.