Guideline topic: Pharmacological management of asthma
Evidence table 4.2: Ipratopium bromide

Author

Year

Study type

Quality rating

Population

Outomes measured

Effect size

Confidence intervals / p values

Comments

Adults

Bariffi¹

1986

Randomised, comparing duovent (fenoterol plus ipratropium) vs placebo

+

20 asthmatics with asthma and 20% reversibility.

FEV1

At 30 min, increase of 26.2%

P< 0.01

Not addressing issue of ipratropium alone

Elwood and Abboud²

1982

Double-blind randomised, cross over except for 6^th visit, comparing fenoterol, ipratropium and combination.

+

10 patients with chonic asthma (21-61yrs); 58% pred FEV1; > 20% increase in FEV1 with bagonist; patients on b-agonists, theophylline and BDP

1. FEV1, FVC, FEFV (AUC over 6 hrs)

Imratropium caused 20.1 +-6.6% increase in FEV1 AUC

100 ug Fen plus IPRA 40 ug was similar to 200 ug FENO

P< 0.05

Small study, main interest was effect of combination therapy. Comparison to fenoterol, not a b-agonist used frequently in UK.

Higgins³

1991

Crossover study examining cumulative doses of salbutamol or ipra in double blind, randomised protocol

++

9 patients with asthma and 10 with chronic bronchitis

FEV1 and sGaw

Salbutamol (5,100, 750 and 1000 ug) and ipratropium (similar doses) caused similar max increase in FEV1 (0.58 and 0.59L) in both groups.

Date not applicable

Hockley⁴

1985

IPRA (80, 200, 400 ug) in 9 asthmatics D-blind, randomised, placebo controlled

++

9 asthmatics

FEV1

Max increase in FEV1 was 25% after 80 ug, and 30% fro the two higher doses. Duration was longer for 400ug dose). Max effect by 100 min.

Small numbers. More effect at higher doses.

Hunt⁵

1983

Doses of IPRA of 40, 80, 160 ug on FEV1 in 13 asthmatics, 15 bronchitis

+

FEV1 (peak change)

Changes were 0.51, 0.64, 0.55L for the doses, change sign sustained for 3,6 and 8 hours at the increasing doses.

Study shows the prolonged bronchodilator response with higher doses, although all doses cased similar max response. Small number of patients.

Kreisman⁶

1984

Ipra (40 ug) or theophytlline or both

+

12 asthmatics

FEV1

By 30 min increase in FEV 1 z/fer IPRA was 11.7%

P< 0.05

Small study showing bronchodilator effect, potentiated by theophylline

Burki⁷

1997

Randomised double blind, placebo controlled crossover

+

19 patients aged 15-52 years (mean 27.7)

FEV1 29 – 67 (mean 53.8) % pred.

15 %

reversibility to B2-agonists

No oral steroids

Compared single doses of oral theoph. and inhaled iprat., alone or in combination

1)FEV₁ at 15 min, 30 min, 1 hr, 2 hr….up to 6 hours for each regimen















) Side effects, BP, pulse, ECG

Each regimen resulted in a significant increase in FEV₁

The combined regimen resulted in significantly greater effect FEV₁=3.0 L (iprat.+ theoph.) vs 2.5 L (iprat.) vs 2.6L (theoph.) at 3 hrs post drug

No significant side effects reported for any treatment.

P<0.05














P<0.05

The optimum dose of theoph. was established at screening day 3, to achieve theoph. concentrations

10-20 µg/ml when 10/32 patients screened were excluded.

There were 4 dosage regimes

Regimen A- theoph. + inhaled placebo

Regimen B- oral placebo + inh iprat.

Regimen C- theoph. + inhaled iprat.

Regimen D- oral and inhaled placebo

Note- theophylline short-acting tablets were used

Ruffin⁸

1982

D-bvlind, placebo controlled, single dose of IPRA (60 ug), or feneterol (200 ug) or various combinations of each

++

18 asthmatics (20% increase in Fev 1 with salb)

FEV1

DATA not applicable

Sahlstrom⁹

1986

Fenoterol, IPRA (40 ug) and combination compared in d-blind placebo controlled and cross over.

++

24 adult asthmatics

SGAW FEV1

0.53 L increase after IPRA after 2 hrs

P< 0.001

Small numbers. Comparative study with combination.