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Disclaimer: The following information is fictional and is only
intended for the purposes ofillustrating key concepts for results
data entry in the Protocol Registration System (PRS).
Example Cross-Over Study Design(A Phase II, Randomized,
Double-Blind Crossover Study of
Hypertena and Placebo in Participants with High Blood
Pressure)
Methods
Study Design
This is a single-center, randomized,double-blind
(subject/investigator), 2-waycrossover study design. Enrolled
patientshad high blood pressure being treated at aspecialty clinic
associated with a hospital in
Springfield, IL. The study consisted of twotreatment periods of
2 weeks separated bya washout period of 2 weeks. (Figure 1)The
objective of the study is to determinewhether Hypertena has an
effect onreducing systolic and diastolic bloodpressure in
participants diagnosed with highblood pressure.
The protocol and informed consentdocuments were reviewed and
approved bya recognized ethics review board at the
study facility. The study was performed inaccordance with the
Declaration of Helsinki.
Participants
Inclusion Criteria
Participants, regardless of gender, atleast 18 years of age and
diagnosed withhigh blood pressure based on the averageof two or
more properly measured, seated,blood pressure readings during two
or more
office visitswere eligible for the trial.Participants were
diagnosed with high bloodpressure if the classification was Stage 1
or2 as defined in the Seventh Report of theJoint National Committee
on Prevention,Detection, Evaluation, and Treatment ofHigh Blood
Pressure (JNC 7, NHLBI;
http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf):
Systolic blood
pressure (SBP) 140 mmHg and/ordiastolic blood pressure (DBP) 90
mmHg.Participants were also required to have asufficient level of
education to understandstudy procedures and be able tocommunicate
with site personnel.
Exclusion Criteria
Patients were excluded if they had ahistory of kidney disease;
diabetes; acuteliver injury (e.g., hepatitis) or severecirrhosis;
pregnancy or breast-feeding;allergy to Hypertena or lactose;
history ofdrug or alcohol abuse; or participation in astudy of an
investigational medication withinthe past 30 days.
Participants were randomized in a 1:1ratio to receive either
Hypertena 20 mgtablet or Placebo tablet (matching
Hypertena 20 mg) once daily in the morningin a fasting state for
2 weeks. After 2 weeksof washout, participants crossed over
toreceive the alternative intervention for 2weeks, Placebo tablet
(matching Hypertena20 mg) or Hypertena 20 mg tablet,respectively,
once daily in the morning in afasting state.
Primary EndpointsThe co-primary endpoints were the
change from baseline in mean sitting
systolic and diastolic blood pressure at 2weeks. Blood pressure
was assessed afterthe participant was in a seated position forat
least 5 minutes. Blood pressure wasmeasured with an automated
measurementdevice 3 times at 1 to 2 minute intervals anda mean of
the 3 measurements wascalculated.
http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdfhttp://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdfhttp://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdfhttp://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdfhttp://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf
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Secondary EndpointsThe secondary endpoint was response
rate, with response defined as achieving amean sitting systolic
blood pressure < 140mmHg and a mean sitting diastolic
bloodpressure < 90 mmHg at 2 weeks.
Statistical AnalysisAll participants who received at least
one dose of each intervention andcompleted all study visits were
included inthe efficacy analysis. A sample size of 125participants
was needed to provide 90%power to detect a 5 mmHg difference
insystolic blood pressure. ANCOVA wasused to compare the difference
betweenparticipants receiving Hypertena andPlacebo, with the trough
blood pressure at
baseline, body weight, and age ascovariates, and the treatment
group andstudy site as factors. The test wasperformed with a
significance level of 0.05(two-sided). Statistical analyses
were
carried out using SAS software version 6.12(SAS Institute, Inc.,
Cary, NC, USA).
Adverse Event AssessmentSafety was assessed by the number of
participants with adverse events (AEs).AEs were collected by
systematicassessment using terms from the MedicalDictionary for
Regulatory Activities(MedDRA), version 11.1 in participants
whoreceived one or more doses of intervention.
Adverse events during washout were notcollected.
Results
Of the 200 patients screened foreligibility between May 2008 and
October2008, 65% (N = 130) were randomized tointervention (Figure
1). Of those notrandomized, 35 did not meet inclusioncriteria and
35 declined to participate. Thelast participant completed in
February 2009.
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Table 3. All participants with adverse events during the 2
weekson each intervention*
Hypertenan = 127
Placebon = 127
Cardiac Disorders
Myocardial Infarction** 0 1
Gastrointestinal Disorders
Nausea 10 5
Infections and Infestations
Influenza 2 1
Nervous System Disorders
Dizziness 11 6
Headache 20 16
Restlessness 5 4
Psychiatric Disorders
Depression 1 1
*A participant could have experienced the same adverse event
more than once during the 2 weeksmonitored. 3 participants had more
than one headache while receiving Hypertena, and 1 participant
hadmore than one headache while receiving Placebo.**Event resulted
in hospitalization
