Table 1.
Summary of IM ziprasidone trials.
| Study | Design | Subjects (n) | Dose1 | Main findings |
|---|---|---|---|---|
| Brook et al., 2000 [9] | International multicenter RCT (IM ZIP versus HAL2) 3 d IM then 4 d PO |
(90 versus 42) | 10–80 | No pt in any group had QTc >500 ms ZIP mean QTc change3 in ms: 2.14 (versus 2.22 HAL) |
|
| ||||
| Brook et al., 2005 [1] | International multicenter RCT (IM ZIP versus HAL2) 3 d IM then 6 wk PO |
(427 versus 138) | 10–20 | No pt in any group had QTc >500 ms Mean ZIP endpoint QTc in ms: 389.9 (versus 383.7 HAL) Mean ZIP QTc change2 in ms: 3.2 (versus −3.5 HAL) |
|
| ||||
| Chen et al., 20103 [10] | 7 d open parallel RCT (IM ZIP versus HAL2) |
(40 versus 40) | 10–60 | 1 ZIP pt withdrew after a QTc prolongation |
|
| ||||
| Daniel et al., 2001 [11] | 24 h double-blind RCT | (38 versus 41) | 2, 20 | Mean QTc change3 in ms: 3.5 (2 mg) and −1.3 (20) Maximum QTc recorded was 475 ms |
|
| ||||
| Daniel et al., 2004 [12] | Multicenter RCT (3 IM ZIP doses versus HAL2) 3 d IM, then 4 d PO |
(69, 71, 66, 100 HAL) | 20, 40, 80 | No pt in any group had QTc >500 ms Mean QTc change3 in ms: 0.7 (20 mg), −2.9 (40), and 0.5 (80); −0.5 (HAL) |
|
| ||||
| Emul et al., 2009 [13] | Open-label prospective trial (schizophrenia versus healthy controls; baseline versus 1.4–2 h after IM ZIP |
(11 versus 11) | 20 | IM ZIP did not appear to influence atrial and ventricular electrical conduction in drug-free schizophrenia inpts; schizophrenia may affect atrial conduction resulting in atrial fibrillation |
|
| ||||
| Jiang et al., 20084 [14] | 3 d open parallel-group RCT (IM ZIP versus HAL4) |
(36 versus 35) | 10–40 | No pt in any group had QTc >500 ms |
|
| ||||
| Lesem et al., 2001 [15] | 24 h double-blind RCT | (54 versus 63) | 2, 10 | Mean QTc change3 in ms: −3.7 (2 mg) and −1.8 (10) |
|
| ||||
| Li et al., 20104 [16] | 5 d double-blind parallel-group RTC (IM ZIP versus HAL2) |
(38 versus 37) | 10–30 | 3 pts experienced QTc prolongation (ms): 430, 450 and, 510 |
|
| ||||
| Mautone and Scarone, 2011 [17] | Phase IIIb noncomparative(3 d IM then PO for 8 w) | (150) | 10 | Mean QTc change3 in ms in 3 pts: 110 (2 d), 70 (5 d), and 55 (10 d). 2 pts discontinued due to QTc prolongation |
|
| ||||
| Micelli et al., 2005 [18] | Phase I study in healthy volunteers: single 5, 10, or 20 mg IM dose; HAL2) |
(24) | 5–20 | ZIP and HAL were associated with modest QTc increases |
|
| ||||
| Miceli et al., 2010 [19] | 3 d single-blind parallel-group | (31 versus 27) | 20–30 | Mean QTc change (ms):3 1st IV 4.6 (ZIP) and 6.0 (HAL) 2nd IV 12.8 (ZIP) and 14.7 (HAL) No pt had QTc >480 ms QTc ≥450 ms and QTc changes >60 ms: 2 in ZIP (0 in HAL) |
|
| ||||
| Preval et al., 2005 [20] | Naturalistic study (IM ZIP versus first-generation antipsychotics) | (19 versus 80) | 20 | No patient in the IM ZIP group had QTc >460 ms |
|
| ||||
| Rais et al., 2010 [21] | A 24 h open-label prospective study in geriatric population |
(16) | 10–20 | Mean QTc range in ms: baseline 382.0–429.5 versus trial: 428.1–370.0 |
|
| ||||
| Tambyraja and Strawn, 2011 [4] | Case report (70 yo vascular dementia) | (1♀) | 20 | Patient lost consciousness within 45 min of ZIP IM Pulseless, hypotensive, and poor perfusion signs ECG: bradycardia (30–40 bpm) with 3rd degree block |
|
| ||||
| Li et al., 20104 [16] | 3 d double- or single-blind parallel-group RCT (IM ZIP versus HAL2) | (16 versus 16) | 20–40 | No significant QTc prolongations in ZIP or HAL |
|
| ||||
| Witsil et al., 2012 [2] | Case report (history of substance abuse) | (1♂) | 20 | Baseline ECG showed QT/QTc of 484/475 ms. Palpitations and weakness 45 min after IM ZIP Maximum in repeated ECGs: QT/QTc of 612/517 ms |
|
| ||||
| Yin and Wang, 20124 [22] | 3 d open parallel-group RCT (IM ZIP versus HAL2) | (30 versus 30) | 10–40 | Maximum QTc in ZIP: 461 ms. |
|
| ||||
| Zhang et al., 20134 [7] | 3 d rater-blind, actively-controlled parallel group multicenter RCT (IM ZIP versus HAL2) | (189 versus 187) | 10–40 | ZIP mean QTc change3 in ms: 0.7 (versus −1.6 HAL)5
ZIP: 3 pts with QTC ≥450 ms. None with QTC ≥450 ms HAL: 2 pts with QTC ≥480 ms and 1 with QTC ≥500 ms |
bpm: beats per minute; d: day; ECG: electrocardiogram; h: hour; HAL: haloperidol; inpts: inpatients; IM: intramuscular;
IV: intravenous; min: minutes; ms: milliseconds; PO: by mouth; pt: patient; RCT: randomized controlled trial; QTc: QTc interval; wk: week; yo: year-old; ZIP: ziprasidone.
1Ziprasidone dose in mg/day.
2HAL dose ranged from 5 to 20 mg/day in the various studies.
3QTc change from baseline to end of treatment.
4In Chinese.
5Effect size of the mean difference = 0.009. It was calculated using Cohen's method [23].