Handle is some sort of identifier for characters/items in the game. I haven't really used it myself so I don't know a ton about it.
So you could do something like this:
IF
CharacterEnteredTrigger(_Player,TRIGGER_Fort_WatchLocked)
AND
GetItemhandleForItemTemplateInInventory(_Player,"WPN_Undead_Pickaxe_A_0f11d7e7-4e0b-4921-aa63-f8c6511ac631",_Handle)
THEN
CharacterEquipItemhandle(_Player,_Handle);
That would equip the template specified by checking your inventory for that template, grabbing the handle of it, and then the call can grab that handle.
On the surface it seems like a way to manipulate non-global items similar to how you can use GUID.
One of the things about handles I'm not sure about is how do you know what the handle is of an item before you want to use it. The only way I can see is using one of the queries but that seems to limit your options in using them.
Usually in cases like this if I don't know exactly what Larian does with these things I'll go spelunking in MAIN to see if they use it at all. Larian seems to use it for thievery especially. When you steal a specific object from someone and they catch you they can reference the handle and move it back to the NPC who owns it.
Example:
IF
CharacterSpottedItemTheft_Redhanded(_Offender,_Spotter,_Owner,_Object,_Value,_Handle,_CrimeID,_X,_Y,_Z,_Pitch,_Yaw,_Roll,_Container)\
THEN
ItemHandleToCharacter(_Handle,_Owner,1);
Or here's a pretty simple one, this one "consumes" a skill book by removing it after use.
IF
CharacterUsedItemTemplate(_Player, "BOOK_Skill_StatPoints_28b2ff38-74dd-494a-8a34-9020ecca47b1", _Handle)
THEN
CharacterAddAttributePoint(_Player, 1);
ItemHandleDelete(_Handle);
CharacterPlayEffect(_Player, "FX_GP_Level_Up_A");