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CHIPS trial "Control of Hypertension In Pregnancy Study"
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CHIPS Trial — Control of Hypertension In Pregnancy Study
Overview
The CHIPS Trial (Control of Hypertension In Pregnancy Study) is a landmark international, open-label, multicenter randomized controlled trial that compared "less-tight" versus "tight" blood pressure control in pregnant women with non-severe hypertension. The primary publication appeared in the New England Journal of Medicine in 2015 (Magee et al., NEJM 2015, PMID: 25629739).
Background & Rationale
Before CHIPS, there was genuine equipoise about whether actively treating mild-to-moderate hypertension in pregnancy was beneficial or harmful. Concerns existed that tight control might reduce uteroplacental perfusion, increasing the risk of fetal growth restriction (SGA babies), while leaving blood pressure less controlled risked progression to severe hypertension and maternal end-organ damage.
Study Design
| Feature | Detail |
|---|---|
| Design | Open, international, multicenter RCT |
| Population | Pregnant women at 14w0d – 33w6d gestation |
| Eligible BP | Office diastolic BP 90–105 mmHg (or 85–105 if already on antihypertensives) |
| Hypertension type | Non-proteinuric preexisting (chronic) or gestational hypertension |
| Sample size | 987 women (493 less-tight; 488 tight) |
| Preexisting hypertension | 74.6% of participants |
| Gestational hypertension | ~25% of participants |
| Funding | Canadian Institutes of Health Research |
| Trial registration | ISRCTN71416914 / NCT01192412 |
Intervention: The Two Arms
| Arm | Target Diastolic BP |
|---|---|
| Less-tight control | Target DBP 100 mmHg |
| Tight control | Target DBP 85 mmHg |
- Drug of choice was labetalol; methyldopa was also used and did not result in inferior outcomes
- Management followed a structured antihypertensive algorithm
- Mean DBP achieved in less-tight group was ~4.6 mmHg higher than tight group (p <0.001)
- Tight group achieved a mean BP of approximately 133/85 mmHg
Outcomes
Primary Outcome (Perinatal)
Composite: pregnancy loss OR high-level neonatal care >48 hours in the first 28 postnatal days
| Outcome | Less-Tight (n=493) | Tight (n=488) | Adjusted OR (95% CI) |
|---|---|---|---|
| Primary composite | 31.4% | 30.7% | 1.02 (0.77–1.35) — NS |
| Pregnancy loss | 3.0% | 2.7% | 1.14 (0.53–2.45) |
| High-level neonatal care >48h | 29.4% | 29.0% | 1.00 (0.75–1.33) |
| SGA (<10th percentile) | 16.1% | 19.7% | 0.78 (0.56–1.08) |
| Preterm birth | 35.6% | 31.5% | p=0.18 |
| Placental abruption | 2.2% | 2.3% | 0.94 (0.40–2.21) |
No significant difference in primary perinatal outcome between groups.
Secondary Outcome (Maternal)
Serious maternal complications up to 6 weeks postpartum
| Maternal Outcome | Less-Tight | Tight | OR/p-value |
|---|---|---|---|
| Serious maternal complications | 3.7% | 2.0% | 1.74 (0.79–3.84) — NS |
| Severe hypertension (≥160/110) | 40.6% | 27.5% | p <0.001 ✦ |
| Preeclampsia | 48.9% | 45.7% | 1.14 (0.88–1.47) |
| Platelets <100×10⁹/L | 4.3% | 1.6% | 2.63 (1.15–6.05) ✦ |
| Elevated AST/ALT with symptoms | 4.2% | 1.8% | 2.33 (1.05–5.16) ✦ |
| HELLP syndrome | 1.8% | 0.4% | 4.35 (0.93–20.35) |
✦ = statistically significant
Key Findings & Interpretation
- Perinatal safety was equivalent — tight BP control did not cause fetal harm (no increase in SGA or pregnancy loss).
- Less-tight control caused significantly more severe hypertension — a 40.6% vs. 27.5% rate, with ~13% absolute risk increase.
- Serious maternal complications — numerically higher in less-tight group but did not reach statistical significance (possibly underpowered for this endpoint).
- Post-hoc analysis showed that severe hypertension, independent of preeclampsia, was independently associated with serious maternal complications.
- No gestational age at initiation at which less-tight control was superior to tight control.
- Child developmental outcomes at 12-month follow-up showed no evidence of developmental programming of growth.
- Cost — less-tight control tended to be ~CAD $6,000 more expensive (p=0.07), driven by neonatal care costs.
Clinical Significance & Guideline Impact
The CHIPS trial provided strong evidence that:
- Women with non-severe pregnancy hypertension should receive tight BP control (target DBP ~85 mmHg)
- Tight control does not increase the risk of small-for-gestational-age infants as previously feared
- Less-tight control leads to significantly more severe hypertension, which carries maternal risk (HELLP, liver injury, thrombocytopenia)
This shifted clinical practice away from the traditional permissive approach (allowing DBP up to 100 mmHg) and is now incorporated into major obstetric and nephrology guidelines.
Brenner and Rector's The Kidney, 2-Volume Set, Table 48.5; Rosen's Emergency Medicine, Chapter references; Goodman & Gilman's Pharmacological Basis of Therapeutics
Primary citation: Magee LA et al. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med. 2015;372:407–417. PMID: 25629739
Summary publication: Magee LA et al. Management of non-severe pregnancy hypertension — A summary of the CHIPS Trial. Pregnancy Hypertens. 2019 Oct. PMID: 31627057
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