A randomised pragmatic trial of corticosteroid optimization in severe asthma using a composite biomarker algorithm to adjust corticosteroid dose versus standard care: study protocol for a randomised trial

Hanratty, Catherine E.; Matthews, John G.; Arron, Joseph R.; Choy, David F.; Pavord, Ian D.; Bradding, P.; Brightling, Christopher E.; Chaudhuri, Rekha; Cowan, Douglas C.; Djukanovic, Ratko; Gallagher, Nicola; Fowler, Stephen J.; Hardman, Tim C.; Harrison, Tim; Holweg, Cécile T.; Howarth, Peter H.; Lordan, James; Mansur, Adel H.; Menzies-Gow, Andrew; Mosesova, Sofia; Niven, Robert M.; Robinson, Douglas S.; Shaw, Dominick E.; Walker, Samantha; Woodcock, Ashley; Heaney, Liam G.

doi:10.1186/s13063-017-2384-7

Trials

Table 3 Treatment steps for biomarker-based therapy adjustment

From: A randomised pragmatic trial of corticosteroid optimization in severe asthma using a composite biomarker algorithm to adjust corticosteroid dose versus standard care: study protocol for a randomised trial

Steroid therapy step	Seretide MDI	Seretide Accuhaler	Symbicort Turbohaler	Flutiform MDI	Relvar Ellipta	Other LABA/ICS combinations (FP equivalent dose per day)
Step 1	Seretide 50 2 bd	Seretide 100 1 bd	Symbicort 6/200 1 bd If ACQ ≥ 1.5 add OXIS 12 1 bd (or equivalent)	Flutiform 50 2 bd If ACQ ≥ 1.5 add OXIS 12 1 bd (or equivalent)	Seretide 100 Accuhaler 1 bd	LABA/FP equivalent – 200 μg per day
Step 2	Seretide 125 2 bd	Seretide 250 1 bd	Symbicort 6/200 2 bd If ACQ ≥ 1.5 add OXIS 12 1 bd (or equivalent)	Flutiform 125 2 bd If ACQ ≥ 1.5 add OXIS 12 1 bd (or equivalent)	Relvar 22/92 1 mane	LABA/FP equivalent – 500 μg per day
Step 3	Seretide 250 2 bd	Seretide 500 1 bd	Bud 12/400 2 bd	Flutiform 250 2 bd	Relvar 22/184 1 mane	LABA/FP equivalent – 1000 μg per day
Step 4	Seretide 250 2 bd μg Prednisolone 5 mg per day	Seretide 500 1 bd Prednisolone 5 mg per day	Bud 12/400 2 bd Prednisolone 5 mg per day	Flutiform 250 2 bd Prednisolone 5 mg per day	Relvar 22/184 1 mane Prednisolone 5 mg per day	LABA/FP equivalent – 1000 μg per day Prednisolone 5 mg per day
Step 5	Seretide 250 2 bd Prednisolone 10 mg per day	Seretide 500 1 bd Prednisolone 10 mg per day	Bud 12/400 2 bd Prednisolone 10 mg per day	Flutiform 250 2 bd Prednisolone 10 mg per day	Relvar 22/184 1 mane Prednisolone 10 mg per day	LABA/FP equivalent – 1000 μg per day Prednisolone 10 mg per day
Step 6	Seretide 250 2 bd Prednisolone 15 mg per day	Seretide 500 1 bd plus Prednisolone 15 mg per day	Bud 12/400 2 bd plus Prednisolone 15 mg per day	Flutiform 250 2 bd Prednisolone 15 mg per day	Relvar 22/184 1 mane plus Prednisolone 15 mg per day	LABA/FP equivalent – 1000 μg per day plus Prednisolone 15 mg per day
Step 7*	Seretide 250 2 bd Prednisolone 20 mg per day	Seretide 500 1 bd Prednisolone 20 mg per day	Bud 12/400 2 bd Prednisolone 20 mg per day	Flutiform 250 2 bd Prednisolone 20 mg per day	Relvar 22/184 1 mane Prednisolone 20 mg per day	LABA/FP equivalent – 1000 μg per day plus Prednisolone 20 mg per day

* It is recognised that on some occasions patients may require higher doses of systemic steroids beyond 20 mg prednisolone per day; as with all treatment steps, particular attention should be paid to adherence with prednisolone, but if required prednisolone can be increased in further 5 mg increments
The therapeutic adjustments are designed to reflect clinical practice and to be pragmatic and allow accommodation of currently used combination inhaler therapies in this population; because of this, ICS will be adjusted in line with the patient’s prescribed LABA/ICS inhaler device. This will mean in some situations that LABA is adjusted along with ICS which would reflect usual clinical practice
If patient is on theophylline, leukotriene receptor antagonist, at baseline, these are not adjusted during study; they are not added during the study
If patient has an Asthma Control Questionnaire (ACQ)7 > 1.5 and corticosteroid is not increased, tiotropium should be added if no contraindications if patient is not already on Long-Acting Muscarinic Antagonist (LAMA) therapy or nebulised short-acting anti-muscarinic therapy
If on inhaled steroid monotherapy (nebulised or inhaled) in addition to ICA/LABA combination therapy, the inhaled steroid monotherapy will be withdrawn initially
If a patient is on oral steroids and reduces to 5 mg per day, they should be advised to omit their prednisolone on the morning of their next study visit; at that visit, they should have a morning cortisol checked locally as part of routine clinical care: if cortisol within normal range of local laboratory reference value, steroids can be stopped completely if indicated by study algorithm; if cortisol is present but outside normal reference range of local laboratory, gradual oral steroid withdrawal in 1 mg increments is carried out; if cortisol is undetectable, prednisolone is maintained at 5 mg for study duration
bd twice a day, Bud budesonide, FP fluticasone propionate, ICS inhaled corticosteroid, LABA long-acting beta agonist, mane every morning, MDI metered dose inhaler

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ISSN: 1745-6215

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