Table 2.
Grade 4 and serious AEs and ARs
| Abacavir | Nevirapine | |||
|---|---|---|---|---|
| Events | Reactions* | Events | Reactions* | |
| Total SAE/SAR | 15 | 6 [3]† | 22 | 14 [4]† |
| Grade 4 | 7 | [2] | 11 | 5 [2] |
| Suspected HSR | 4 | 4 | ||
| Acute asymptomatic hepatitis (LFTs) | 1 | 1 | ||
| Anaemia | 4 | 3 | [1] | |
| Pancytopenia + haematemesis | 1 | [1] | ||
| Sepsis + haematemesis | 1 | [1] | ||
| Deep vein thrombosis | 1 | [1] | ||
| Head injury | 1 | |||
| Indeterminate cerebral disease | 1 | |||
| Urticarial rash + fever + mucosal symptoms | 1§ | |||
| Grade 1–3 | 7 | 6 | 10 | 9 [1] |
| Suspected HSR | 6 | 6 | 9 | 9 |
| Duodenal ulcer + haematemesis | 1 | |||
| Fever + constitutional symptoms | 1¶ | [1¶] | ||
| Death from unknown cause | 1 | [1] | 1 | [1] |
| Participants with at least one SAE/SAR (% of randomized‡) | 14 (5%) | 6 (2%) | 22 (7%) | 14 (5%) |
| Rate (events per 100 person years) | 11.4 | 4.6 | 17.7 | 11.2 |
| Grade 4 AE/AR not reported as SAE/SAR (not reviewed) | 73 | [11] | 105 | [11] |
| Anaemia (<6.5 g/dl) | 14 | 13 | ||
| Neutropenia (<0.5 × 109/l) | 47 | [9] | 73 | [11] |
| Leucopenia (<1.0 × 109/l) | 5 | 5 | ||
| Thrombocytopenia (<20 × 109/l) | 1 | 1 | ||
| Raised bilirubin (>5.0 × ULN) | 2 | 3 | ||
| Raised creatinine (>6.0 × ULN) | 1 | |||
| Raised liver enzymes (>10.0 × ULN) | 7 | |||
| Hyponatraemia (<116 mmol/l) | 1 | 1 | ||
| Myopathy | 1 | (1) | ||
| Paralytic ileus | 1 | |||
| Convulsions | 2 | (1) | ||
| Participants with at least one grade 4 AE/ARnot reported as SAE/SAR (% of randomized‡**) | 61 (20%) | 11 (4%) | 92 (31%) | 11 (4%) |
| Total grade 4 AE/AR (including grade 4 SAE/SAR) | 80 | 13 | 116 | 18 |
| Rate (events per 100 PY) | 60.7 | 9.9 | 93.2 | 14.5 |
| Participants with at least one grade 4 AE/AR (% of randomized‡) | 65 (22%) | 13 (4%) | 98 (32%) | 18 (6%) |
Grade 4 AE are new grade 4 AE reported during the first 24 weeks which were not pre-existing at randomization and excluding recurrences of the same event. Grade 4 laboratory results are returned to clinicians (in both LCM and CMO arms, see Methods), but there was no requirement to report a clinical or laboratory grade 4 AE as an SAE unless the event met the ICH-GCP criteria for SAE.
SAE, serious adverse event; SAR, serious adverse reaction; HSR, hypersensitivity reaction.
Definitely/probably related or uncertain whether related to blinded trial drugs.
For SAE: number of confirmed SARs at independent SAE review [additional SAE originally reported by the clinical investigator as uncertain whether related to blinded trial drugs, but judged unlikely to be related or unrelated to blinded trial drugs at independent review]. For grade 4 AE (not reviewed): [any grade 4 event reported by the clinical investigator as definitely/probably related or uncertain whether related to blinded trial drugs].
600 randomized, 300 to abacavir and 300 to nevirapine.
Related to open label nevirapine following discontinuation of blinded abacavir for a previous HSR.
Considered uncertain whether related to rabies vaccination on independent review but unlikely to be related to blinded trial drug.
Participants with SAE reported could have laboratory Grade 4 AE at the same time which did not meet ICH-GCP SAE criteria.