As for me: I haven't figured it out yet, sometimes a fractional scale works, sometimes you get vague errors. In any case what I have noticed is that quality drops significantly if you use fractionals.

For my set-up at home (1080 - 4k - 1080) I have a simple script, that really was more of a `write once - use always`-experience. E.g.

    xrandr --output HDMI1 --auto --scale 2x2 --pos 0x0+0+0
    xrandr --output eDP1 --auto --scale 2x2 --pos 7680x0+0+0
    xrandr --output DP1 --auto --mode 3840x2160 --scale 1x1 --pos 3840x0+0+0 --primary

So basically what I do is, I virtually up-scale my other screens up to 4k, such that system-wide zoom settings are (more or less) consistent and enjoyable.