Lambrichts 2019 — LADIES DIVA Trial

Citation: Lambrichts DPV, Vennix S, Musters GD, et al; on behalf of the LADIES trial collaborators. Hartmann’s procedure versus sigmoidectomy with primary anastomosis for perforated diverticulitis with purulent or faecal peritonitis (LADIES): a multicentre, parallel-group, randomised, open-label, superiority trial. Lancet Gastroenterol Hepatol. 2019;4:599-610. doi:10.1016/S2468-1253(19)30174-8.

Study design

• DIVA arm of the LADIES trial (LOLA arm — lavage vs. sigmoidectomy — reported separately, see Vennix 2015 - Ladies Trial LOLA). Multicenter (8 academic + 34 teaching hospitals; Belgium, Italy, Netherlands), open-label RCT, randomized 1:1.
• Population: Hinchey III or IV perforated diverticulitis (purulent or faecal peritonitis) — unlike LOLA/SCANDIV, this trial includes fecal peritonitis. Excluded: dementia, previous sigmoidectomy, previous pelvic radiotherapy, high-dose steroids (≥20mg/day), age outside 18-85, preoperative shock needing inotropic support.
• Intervention: Hartmann’s procedure (resection + end colostomy) vs. sigmoidectomy with primary anastomosis (± defunctioning ileostomy, surgeon’s discretion).
• Primary endpoint: 12-month stoma-free survival. Secondary: short-term morbidity/mortality (index and reversal procedures separately), QoL.
• 133 patients randomized (93 Hinchey III, 40 Hinchey IV) between Jul 2010 and Jun 2016; trial terminated early for slow accrual (not a safety stop, unlike LOLA). Modified ITT: 66 Hartmann’s / 64 primary anastomosis (92 Hinchey III, 38 Hinchey IV).

Key findings

Outcome	Hartmann’s (n=66)	Primary anastomosis (n=64)	p / HR
12-month stoma-free survival	71.7% (95% CI 60.1-83.3)	94.6% (95% CI 88.7-100)	HR 2.79 (1.86-4.18), log-rank p<0.0001
— Hinchey III subgroup	79.8%	95.3%	HR 2.35 (1.49-3.71), p=0.00025
— Hinchey IV subgroup	51.9%	92.2%	HR 4.15 (1.71-10.1), p=0.0016
Short-term major morbidity (index)	12% (8)	14% (9)	p=0.80
Short-term mortality (index)	3% (2)	6% (4)	p=0.44
Post-reversal overall morbidity	30% (13/44)	8% (3/38)	p=0.023
Combined (index+reversal) mortality	3% (2)	6% (4)	p=0.21

• Age subgroup: benefit of primary anastomosis held regardless of age (HR 2.35 for <60y, HR 3.41 for ≥60y).
• Stoma reversal rate: 68% (44/65 with a stoma) after Hartmann’s vs. 83% (38/46) after primary anastomosis (p=0.085) — not significant, but numerically favors primary anastomosis; reversal after primary anastomosis (mostly simple ileostomy closure, 89% of reversals) was faster (median 113.5 vs 133.0 days) and had a shorter postoperative stay (4.0 vs 5.0 days) than Hartmann’s colostomy reversal.
• No significant QoL differences between groups after correction for multiple testing.
• Overall (index + reversal combined) morbidity trended lower with primary anastomosis (40% vs 56%, p=0.078) though not significant; overall mortality similar (6% vs 3%, absolute difference small, only 4 vs 2 patients).

Limitations

• Premature termination due to slow accrual (not the planned 236 patients) — same practical problem (emergency-setting RCT recruitment) affecting essentially all trials in this space (SCANDIV, Ladies LOLA). Despite this, the primary endpoint was still significant, partly because the original power calculation assumed only 90% power.
• Possible selection bias from surgeon/patient treatment preferences in the narrow emergency decision window — mitigated somewhat by a chart review of 235 eligible non-included patients showing similar (slightly worse) baseline severity, suggesting the trial population wasn’t meaningfully healthier than eligible non-participants.
• Preoperative CT-based Hinchey staging is not highly accurate — diagnostic laparoscopy (used in this trial) gives more accurate Hinchey III/IV distinction than prior trials that randomized before surgery, a methodological strength relative to earlier studies.

Relevance

Completes the Ladies Trial picture (both LOLA and DIVA arms now ingested) and is the wiki’s first source covering Hinchey IV (fecal peritonitis) disease. Answers a different clinical question than SCANDIV Trial/LOLA (which compare lavage vs. resection): given that resection is happening, should it include primary anastomosis or end with a stoma (Hartmann’s)? Clear, large-effect-size answer favoring primary anastomosis in appropriately selected (hemodynamically stable, immunocompetent, <85yo) patients — one of the more decisive findings in this wiki so far, in contrast to the more nuanced/contested lavage-vs-resection question.