Wollersheim 1991.

Methods	Study design: Double‐blind, placebo‐controlled, randomised, cross‐over trial. Trial duration: 11 weeks (3 weeks run‐in, 3 weeks treatment/placebo, 2 weeks wash‐out, 3 weeks treatment/placebo). Method of randomisation: Delivered "at random" but method not described. Concealment of randomisation: Allocation per participant provided in sealed envelope. No further information. Exclusions post‐randomisation: 0 Losses to follow‐up: 7 (due to incomplete diary data, but unclear if primary or secondary). 3 with primary Raynaud's phenomenon withdrew due to side effects.
Participants	Country: Netherlands. Setting: Hospital outpatient clinic, season not stated. No: 16 with primary Raynaud's phenomenon (total no: 25; 9 with secondary Raynaud's). Age: Restricted to 18 ‐ 65 years of age. No breakdown for primary Raynaud's participants. Sex: No breakdown for primary Raynaud's participants. Other: No smoking data for primary Raynaud's participants. Inclusion: Raynaud's phenomenon according to Allen and Brown criteria (Allen 1932), at least 1 attack per day, normal body habitus, normal electrocardiogram and normotensive. Exclusion: Concomitant medications, vasoactive medications during 4 weeks prior to baseline, causes of Raynaud's other than connective tissue disease. Primary Raynaud's definition: Allen and Brown criteria (Allen 1932).
Interventions	Treatment: 30 mg nicardipine 3 times a day. Control: Matching placebo. Duration: 2 x 3 weeks. Wash‐out period: 3 weeks with no drug treatment. Run‐in period: 3 weeks baseline observation with no vasoactive drug treatment.
Outcomes	1. Daily Raynaud's attack rate. 2. Duration of Raynaud's attack in minutes. 3. Severity of Raynaud's attacks on an 11‐point (0 ‐ 10) scale. 4. Participant assessment of drug effectiveness on a 5‐point scale (much worse, worse, no difference, better, much better). 5. Participant and investigator opinion of ischaemic changes on a 3‐point scale (worse, no difference, better). 6. Participant assessment of side effect severity and frequency on a visual analogue scale, to produce an adverse effect score. 7. Participant preference. 8. Response to finger cooling test as measured by systolic and diastolic blood pressure, heart rate, ECG and ECG‐triggered venous occlusion plethysmography, finger skin temperature, laser Doppler flux and transcutaneous oxygen tension.
Notes	3 (all with primary Raynaud's) withdrew with side effects. Mean values for Raynaud's attack rate, duration, severity and adverse effects number given for primary Raynaud's participants. However, no participant preference data or finger cooling test data beyond (for finger cooling) a statement that there was no difference found between primary and secondary Raynaud's phenomenon participants.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Delivered "at random" but method not described.
Allocation concealment (selection bias)	Unclear risk	Double‐blind. Allocation method partially described; allocation per participant provided in sealed envelope. No further information.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind. No further information.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Majority of outcomes participant‐reported. Participants blinded to treatment allocation.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	All data for a given participant excluded from analysis if data missing in any phase. 7 excluded due to missing data but unclear how many had primary Raynaud's phenomenon.
Selective reporting (reporting bias)	Unclear risk	Most but not all outcomes reported.
Other bias	Low risk	None noted.

ANA: antinuclear antibody
 ECG: electrocardiogram/graphic